dinoprost and Adenocarcinoma

Prostaglandin F(2α) (PGF(2α)) is an inflammatory mediator which signals through a G-protein coupled receptor, the F-prostanoid (FP) receptor. We have previously shown elevated FP receptor expression in endometrial adenocarcinoma, a common gynaecological malignancy in Western countries. In this study, the expression of the chemokine CC motif Ligand 20 (CCL20) was determined to be regulated by PGF(2α)-FP receptor signalling in endometrial adenocarcinoma explants and cell line, and expression of CCL20 and its receptor CCR6 was elevated in endometrial adenocarcinoma compared to non-malignant endometrium. Both CCL20 and CCR6 were localised to neoplastic endometrial epithelial cells. The induction of CCL20 expression by PGF(2α)-FP signalling in an endometrial adenocarcinoma cell line stably expressing the FP receptor (FPS cells) was found to be dependent on the intracellular signalling of Gq, EGFR, ERK, calcineurin and nuclear factor of activated T-cells (NFAT) proteins. The treatment of FPS cells with recombinant CCL20 caused a significant increase in proliferation. Therefore these data demonstrate a role for the FP receptor in regulation of the chemokine CCL20, which can mediate proliferation of endometrial adenocarcinoma epithelial cells.

Topics: Adenocarcinoma; Cell Line, Tumor; Cell Proliferation; Chemokine CCL20; Dinoprost; Endometrial Neoplasms; Female; Gene Expression Regulation, Neoplastic; Humans; Intracellular Space; Models, Biological; Protein Transport; Receptors, CCR6; Receptors, Prostaglandin; RNA, Messenger; Signal Transduction

The aim of the present study was to assess the effects of zinc or copper and polyphenolic compounds on the 8-isoprostaglandin F2α concentration in the serum and urine of rats with mammary cancer (adenocarcinoma) induced with 7,12-dimethylbenz[a]antracene. The research focused on the kinetics of alterations in urinary 8-isoPGF2α at the early stage of carcinogenesis as well as the influence of dietary factors on the process. The impact of selected compounds on the intensity of DMBA--induced carcinogenesis was also assessed.. Administration of DMBA, a compound that inducers mammary tumors in experimental animals, increased the serum and urinary 8-isoPGF2α levels in study rats. In the rat model, diet supplementation with zinc, combined with selected polyphenolic compounds (resveratrol or genistein) yielded a statistically significant decrease in the rat serum and urinary biomarker concentration with a simultaneously significant stimulation of carcinogenesis.The results indicate that there is an inverse correlation between the intensity of DMBA-induced carcinogenicity and the level of 8-isoPGF2α in urine and serum of rats.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Adenocarcinoma; Animals; Biomarkers, Tumor; Carcinogens; Copper; Dietary Supplements; Dinoprost; Female; Genistein; Mammary Neoplasms, Experimental; Prognosis; Rats; Rats, Sprague-Dawley; Resveratrol; Stilbenes; Zinc

An increase in cancer cell invasion and microvascular density is associated with a poorer prognosis for patients with endometrial cancer. In endometrial adenocarcinoma F-prostanoid (FP) receptor expression is elevated, along with its ligand prostaglandin (PG)F2α, where it regulates expression and secretion of a host of growth factors and chemokines involved in tumorigenesis. This study investigates the expression, regulation and role of a disintegrin and metalloproteinase with thrombospondin repeat 1 (ADAMTS1) in endometrial adenocarcinoma cells by PGF2α via the FP receptor.. Human endometrium and adenocarcinoma tissues were obtained in accordance with Lothian Research Ethics Committee guidance with informed patient consent. Expression of ADAMTS1 mRNA and protein in tissues was determined by quantitative RT-PCR analysis and immunohistochemistry. Signal transduction pathways regulating ADAMTS1 expression in Ishikawa cells stably expressing the FP receptor to levels seen in endometrial cancer (FPS cells) were determined by quantitative RT-PCR analysis. In vitro invasion and proliferation assays were performed with FPS cells and human umbilical vein endothelial cells (HUVECs) using conditioned medium (CM) from PGF2α-treated FPS cells from which ADAMTS1 was immunoneutralised and/or recombinant ADAMTS1. The role of endothelial ADAMTS1 in endothelial cell proliferation was confirmed with RNA interference. The data in this study were analysed by T-test or ANOVA.. ADAMTS1 mRNA and protein expression is elevated in endometrial adenocarcinoma tissues compared with normal proliferative phase endometrium and is localised to the glandular and vascular cells. Using FPS cells, we show that PGF2α-FP signalling upregulates ADAMTS1 expression via a calmodulin-NFAT-dependent pathway and this promotes epithelial cell invasion through ECM and inhibits endothelial cell proliferation. Furthermore, we show that CM from FPS cells regulates endothelial cell ADAMTS1 expression in a rapid biphasic manner. Using RNA interference we show that endothelial cell ADAMTS1 also negatively regulates cellular proliferation.. These data demonstrate elevated ADAMTS1 expression in endometrial adenocarcinoma. Furthermore we have highlighted a mechanism whereby FP receptor signalling regulates epithelial cell invasion and endothelial cell function via the PGF2α-FP receptor mediated induction of ADAMTS1.

Topics: ADAM Proteins; ADAMTS1 Protein; Adenocarcinoma; Adult; Aged; Apoptosis; Blotting, Western; Calmodulin; Cell Adhesion; Cell Movement; Cell Proliferation; Cells, Cultured; Culture Media, Conditioned; Dinoprost; Endometrial Neoplasms; Endometrium; Endothelium, Vascular; Female; Fluorescent Antibody Technique; Humans; Immunoenzyme Techniques; Middle Aged; NFATC Transcription Factors; Receptors, Prostaglandin; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; RNA, Small Interfering; Signal Transduction; Umbilical Veins; Young Adult

We investigated the effects of a gamma-tocopherol-rich mixture of tocopherols (gamma-TmT, containing 57% gamma-T, 24% delta-T, and 13% alpha-T) on colon carcinogenesis in azoxymethane (AOM)/dextran sulfate sodium (DSS)-treated mice. In experiment 1, 6-week-old male CF-1 mice were given a dose of AOM (10 mg/kg body weight, i.p.), and 1 week later, 1.5% DSS in drinking water for 1 week. The mice were maintained on either a gamma-TmT (0.3%)-enriched or a standard AIN93M diet, starting 1 week before the AOM injection, until the termination of experiment. In the AOM/DSS-treated mice, dietary gamma-TmT treatment resulted in a significantly lower colon inflammation index (52% of the control) on day 7 and number of colon adenomas (9% of the control) on week 7. gamma-TmT treatment also resulted in higher apoptotic index in adenomas, lower prostaglandin E2, leukotriene B4, and nitrotyrosine levels in the colon, and lower prostaglandin E2, leukotriene B4, and 8-isoprostane levels in the plasma on week 7. Some of the decreases were observed even on day 7. In experiment 2 with AOM/DSS- treated mice sacrificed on week 21, dietary 0.17% or 0.3% gamma-TmT treatment, starting 1 week before the AOM injection, significantly inhibited adenocarcinoma and adenoma formation in the colon (to 17-33% of the control). Dietary 0.3% gamma-TmT that was initiated after DSS treatment also exhibited a similar inhibitory activity. The present study showed that gamma-TmT effectively inhibited colon carcinogenesis in AOM/DSS-treated mice, and the inhibition may be due to the apoptosis-inducing, anti-inflammatory, antioxidative, and reactive nitrogen species-trapping activities of tocopherols.

Topics: Adenocarcinoma; Adenoma; Animals; Antioxidants; Apoptosis; Azoxymethane; Carcinogens; Cell Transformation, Neoplastic; Cocarcinogenesis; Colon; Colonic Neoplasms; Dextran Sulfate; Dinoprost; Dinoprostone; Dose-Response Relationship, Drug; gamma-Tocopherol; Inflammation; Leukotriene B4; Male; Mice; Tyrosine

The prostaglandin F(2alpha) (PGF(2alpha)) receptor (FP) is elevated in endometrial adenocarcinoma. This study found that PGF(2alpha) signaling via FP regulates expression of chemokine (C-X-C motif) ligand 1 (CXCL1) in endometrial adenocarcinoma cells. Expression of CXCL1 and its receptor, CXCR2, are elevated in cancer tissue compared with normal endometrium and localized to glandular epithelium, endothelium, and stroma. Treatment of Ishikawa cells stably transfected with the FP receptor (FPS cells) with 100 nmol/L PGF(2alpha) increased CXCL1 promoter activity, mRNA, and protein expression, and these effects were abolished by cotreatment of cells with FP antagonist or chemical inhibitors of Gq, epidermal growth factor receptor, and extracellular signal-regulated kinase. Similarly, CXCL1 was elevated in response to 100 nmol/L PGF(2alpha) in endometrial adenocarcinoma explant tissue. CXCL1 is a potent neutrophil chemoattractant. The expression of CXCR2 colocalized to neutrophils in endometrial adenocarcinoma and increased neutrophils were present in endometrial adenocarcinoma compared with normal endometrium. Conditioned media from PGF(2alpha)-treated FPS cells stimulated neutrophil chemotaxis, which could be abolished by CXCL1 protein immunoneutralization of the conditioned media or antagonism of CXCR2. Finally, xenograft tumors in nude mice arising from inoculation with FPS cells showed increased neutrophil infiltration compared with tumors arising from wild-type cells or following treatment of mice bearing FPS tumors with CXCL1-neutralizing antibody. In conclusion, our results show a novel PGF(2alpha)-FP pathway that may regulate the inflammatory microenvironment in endometrial adenocarcinoma via neutrophil chemotaxis.

Topics: Adenocarcinoma; Animals; Cell Line, Tumor; Cell Movement; Chemokine CXCL1; Chemotaxis, Leukocyte; Dinoprost; Endometrial Neoplasms; Endometrium; Female; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Mice; Mice, Nude; Microscopy, Fluorescence; Neoplasm Transplantation; Neoplasms, Experimental; Neutrophils; Receptors, Interleukin-8B; Receptors, Prostaglandin; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; Transplantation, Heterologous

Pro-inflammatory mediators, like prostaglandin (PG) and chemokines, promote tumourigenesis by enhancing cell proliferation, migration of immune cells and recruitment of blood vessels. Recently we showed elevated expression of the chemokine (C-X-C motif) receptor 2 (CXCR2) in endometrial adenocarcinomas localized to neutrophils and neoplastic epithelial and vascular cells. Furthermore we found that PGF(2alpha)-F-prostanoid (FP) receptor regulates the expression of the CXCR2 ligand CXCL1, to promote neutrophil chemotaxis in endometrial adenocarcinomas. In the present study we identified another CXCR2 ligand, CXCL8 as a target for PGF(2alpha)-FP receptor signalling which enhances epithelial cell proliferation in endometrial adenocarcinoma cells in vitro and in nude mice in vivo. We found that PGF(2alpha)-FP receptor interaction induces CXCL8 expression in endometrial adenocarcinoma cells via the protein kinase C-calcium-calcineurin-NFAT signaling pathway. Promoter analysis revealed that CXCL8 transcriptional activation by PGF(2alpha) signaling is mediated by cooperative interactions between the AP1 and NFAT binding sites. Furthermore, PGF(2alpha) via the FP receptor induced the expression of the regulator of calcineurin 1 isoform 4 (RCAN1-4) via the calcineurin/NFAT pathway in a reciprocal manner to CXCL8. Using an adenovirus to overexpress RCAN1-4, we found that RCAN1-4 is a negative regulator of CXCL8 expression in endometrial adenocarcinoma cells. Taken together our data have elucidated the molecular and cellular mechanism whereby PGF(2alpha) regulates CXCL8 expression via the FP receptor in endometrial adenocarcinomas and have highlighted RCAN1-4 as a negative regulator of CXCL8 expression which may be exploited therapeutically to inhibit CXCL8-mediated tumour development.

Topics: Adenocarcinoma; Animals; Calcineurin; Calcium; Cell Line, Tumor; Dinoprost; Endometrial Neoplasms; Female; Gene Expression Regulation, Neoplastic; Humans; Interleukin-8; Mice; Mice, Nude; Neoplasm Proteins; Neoplasm Transplantation; NFATC Transcription Factors; Protein Kinase C; Receptors, Prostaglandin; Response Elements; Signal Transduction; Transplantation, Heterologous

In endometrial adenocarcinomas COX-2 and F-series prostanoid (FP) receptor expression and prostanoid biosynthesis (PGE(2) and PGF(2alpha)) are elevated. In the present study, we investigated the effect of PGE(2) and PGF(2alpha) on the expression of COX-2 via the FP receptor in endometrial adenocarcinoma cells stably expressing the FP receptor (FPS cells). Using chemical inhibitors of intracellular signaling pathways, reporter gene assays and quantitative RT-PCR analysis, we show that PGE(2) and PGF(2alpha) can mobilize inositol 1,4,5-trisphosphate, induce ERK1/2 phosphorylation via the phospholipase Cbeta-protein kinase A-epidermal growth factor receptor pathway and induce cyclooxygenase-2 (COX-2) expression via the FP receptor. In addition we show that the PGE(2) or PGF(2alpha)-regulation of COX-2 via the FP receptor is mediated via the cAMP response element (CRE) binding site on the COX-2 promoter. These data indicate that PGE(2) and PGF(2alpha) biosynthesized locally within endometrial adenocarcinomas can regulate tumor cell function in an autocrine/paracrine manner via the FP receptor.

Topics: Adenocarcinoma; Cell Line, Tumor; Cyclooxygenase 2; Dinoprost; Dinoprostone; Endometrial Neoplasms; Enzyme Activation; Enzyme Inhibitors; Extracellular Signal-Regulated MAP Kinases; Female; Gene Expression Regulation, Enzymologic; Genes, Reporter; Humans; Inositol 1,4,5-Trisphosphate; Promoter Regions, Genetic; Prostaglandin Antagonists; Receptors, Prostaglandin; Receptors, Prostaglandin E; Response Elements; Signal Transduction; Xanthones

The cytotoxic effects of blattellaquinone (BTQ), a sex pheromone produced by adult female German cockroaches, have been studied using human lung adenocarcinoma A549 cells. 1,4-Benzoquinone (BQ), a toxic chemical implicated in benzene toxicity, was used as a reference compound. Both BQ and BTQ showed comparable toxicity toward A549 cells, with LD50 values estimated to be 14 and 19 microM, respectively. These two compounds increased the formation of an oxidized fluorescent probe, 2',7'-dichlorofluorescein, but had no effect on the cellular GSSG level. Interestingly, BTQ increased the level of 8-epi-prostaglandin F2alpha and was 4-fold more efficient in depleting cellular GSH content than BQ. Of the five GSH adducts of BTQ isolated, three were identified as mono-GSH conjugates, and the other two were di-conjugates. Mass spectrometric and NMR analyses of the di-conjugates showed that the second GSH molecule displaced the isovaleric acid moiety, potentially via a nucleophilic substitution reaction. The ability of BTQ to conjugate a second GSH molecule without quinone regeneration indicated that it may be a more effective cross-linking agent than BQ. Future experiments may be needed to evaluate the overall safety of BTQ before the commercialization of the compound as a cockroach attractant.

Topics: Adenocarcinoma; Animals; Cell Line, Tumor; Cockroaches; Dinoprost; Glutathione Disulfide; Humans; Lung Neoplasms; Magnetic Resonance Spectroscopy; Quinones; Reactive Oxygen Species; Sex Attractants

Prostaglandin (PG) F(2alpha) is a potent bioactive lipid in the female reproductive tract, and exerts its function after coupling with its heptahelical G-protein-coupled receptor [F-series-prostanoid (FP) receptor] to initiate cell signaling and target gene transcription. In the present study, we found elevated expression of fibroblast growth factor (FGF) 2, FGF receptor 1 (FGFR1), and FP receptor, colocalized within the neoplastic epithelial cells of endometrial adenocarcinomas. We investigated a role for PGF(2alpha)-FP receptor interaction in modulating FGF2 expression and signaling using an endometrial adenocarcinoma cell line stably expressing the FP receptor to the levels detected in endometrial adenocarcinomas (FPS cells) and endometrial adenocarcinoma tissue explants. PGF(2alpha)-FP receptor activation rapidly induced FGF2 mRNA expression, and elevated FGF2 protein expression and secretion into the culture medium in FPS cells and endometrial adenocarcinoma explants. The effect of PGF(2alpha) on the expression and secretion of FGF2 could be abolished by treatment of FPS cells and endometrial tissues with an FP receptor antagonist (AL8810) and inhibitor of ERK (PD98059). Furthermore, we have shown that FGF2 can promote the expression of FGF2 and cyclooxygenase-2, and enhance proliferation of endometrial adenocarcinoma cells via the FGFR1 and ERK pathways, thereby establishing a positive feedback loop to regulate neoplastic epithelial cell function in endometrial adenocarcinomas.

Topics: Adenocarcinoma; Adult; Aged; Autocrine Communication; Cell Line, Tumor; Cells, Cultured; Cyclooxygenase 2; Dinoprost; Endometrial Neoplasms; Endometrium; Epithelial Cells; Extracellular Signal-Regulated MAP Kinases; Feedback, Physiological; Female; Fibroblast Growth Factor 2; Gene Expression Regulation, Neoplastic; Humans; MAP Kinase Signaling System; Middle Aged; Paracrine Communication; Receptor, Fibroblast Growth Factor, Type 1; Receptors, Prostaglandin; RNA, Messenger

Type and composition of polyunsaturated fatty acids (PUFAs) are suspected to play an important role in carcinogenesis. Thus we investigated the effects of n-3, n-6 and n-9 PUFAs on tumour growth, liver metastasis and concentration of prostaglandins (PG) and leukotrienes (LT) in experimental ductal pancreatic adenocarcinoma. Ninety male hamsters were randomised into six groups (Gr.) (n=15). While Gr. 1-3 were healthy control groups, Gr. 4-6 weekly received subcutaneous injections of 10mg N-nitrosobis-2-oxypropylamine (BOP)/kg body weight for 12 weeks in order to induce ductal pancreatic adenocarcinoma. Between week 1 and 16 all animals were fed with a standard diet with a raw fat content of 2.9%. In week 17 Gr. 1-6 were allocated to three types of diets: Gr. 1: standard high fat (=SHF diet, rich in n-6 PUFAs)/Gr. 2: FISH-OIL (rich in n-3 PUFAs)/Gr. 3: SMOF (=mixture of n-3, n-6 and n-9 PUFAs)/Gr. 4: BOP+SHF/Gr. 5: BOP+SMOF/Gr. 6: BOP+FISH-OIL. After 32 weeks all animals were sacrificed and pancreas as well as liver were analysed histologically. Furthermore pancreatic and hepatic concentrations of prostaglandins (PGF1alpha, PGE(2)) and LT were measured. FISH-OIL decreased number of macroscopically visible pancreatic tumours (Gr. 4-6: 54.5% vs. 45.5% vs. 9.1%, P<0.05) as well as incidence of liver metastasis (Gr. 4-6: 90.9% vs. 72.7% vs. 36.4%, P<0.05). Furthermore concentration of PGF(1)(alpha), PGE(2) and LT were significantly increased in pancreatic carcinoma compared to tumour-free tissue. Moreover levels of PGF(1)(alpha) and PGE(2) were higher in liver metastasis than in extrametastatic hepatic tissue. However, in Gr. 6 (FISH-OIL) intrametastatic concentration of LT was significantly lower than in non-metastatic hepatic tissue as well as in Gr. 4 and Gr. 5. FISH-OIL decreased number of visible pancreatic tumours and incidence of histological proven liver metastasis. This effect might be caused by a decrease of intrametastatic concentration of LT compared to extrametastatic hepatic tissue.

Topics: Adenocarcinoma; Animals; Cricetinae; Dietary Fats, Unsaturated; Dinoprost; Dinoprostone; Fatty Acids, Unsaturated; Leukotrienes; Liver; Liver Neoplasms; Male; Pancreas; Pancreatic Neoplasms; Prostaglandins

Cyclooxygenase (COX) enzymes catalyze the biosynthesis of eicosanoids, including prostaglandin (PG) F2alpha. PGF2alpha exerts its autocrine/paracrine function by coupling to its G protein-coupled receptor [F-series-prostanoid (FP) receptor] to initiate cell signaling and target gene transcription. In the present study, we found elevated expression of COX-2 and FP receptor colocalized together within the neoplastic epithelial cells of endometrial adenocarcinomas. We investigated a role for PGF2alpha-FP receptor interaction in modulating COX-2 expression and PGF2alpha biosynthesis using an endometrial adenocarcinoma cell line stably transfected with the FP receptor cDNA (FPS cells). PGF2alpha-FP receptor activation rapidly induced COX-2 promoter, mRNA, and protein expression in FPS cells. These effects of PGF2alpha on the expression of COX-2 could be abolished by treatment of FPS cells with an FP receptor antagonist (AL8810) and chemical inhibitor of ERK1/2 kinase (PD98059), or by inactivation of ERK1/2 signaling with dominant-negative mutant isoforms of Ras or ERK1/2 kinase. We further confirmed that elevated COX-2 protein in FPS cells could biosynthesize PGF2alpha de novo to promote a positive feedback loop to facilitate endometrial tumorigenesis. Finally, we have shown that PGF2alpha could potentiate tumorigenesis in endometrial adenocarcinoma explants by inducing the expression of COX-2 mRNA.

Topics: Adenocarcinoma; Aged; Cell Line, Tumor; Dinoprost; DNA, Complementary; Endometrial Neoplasms; Endometrium; Extracellular Signal-Regulated MAP Kinases; Feedback, Physiological; Female; Humans; Middle Aged; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Receptors, Prostaglandin; RNA, Messenger; Signal Transduction; Tissue Distribution; Transfection

Prostaglandins have been implicated in several neovascular diseases. In the present study, we found elevated FP receptor and vascular endothelial growth factor (VEGF) expression colocalized in glandular epithelial and vascular cells lining the blood vessels in endometrial adenocarcinomas. We investigated the signaling pathways activated by the FP receptor and their role in modulating VEGF expression in endometrial adenocarcinoma (Ishikawa) cells. Ishikawa cells were stably transfected with FP receptor cDNA in the sense or antisense orientations. Treatment of Ishikawa cells with prostaglandin F2alpha (PGF2alpha) rapidly induced transphosphorylation of the epidermal growth factor receptor (EGFR) and phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 via the FP receptor. Activation of EGFR-Ras-mitogen-activated protein kinase/ERK kinase (MEK) signaling via the FP receptor resulted in an increase in VEGF promoter activity, expression of VEGF mRNA, and secretion of VEGF protein. These effects of PGF2alpha on the FP receptor could be abolished by treatment of cells with a specific FP receptor antagonist, chemical inhibitors of c-Src, matrix metalloproteinase, and EGFR kinase or by inactivation of signaling with dominant-negative mutant isoforms of EGFR, Ras, or MEK or with small inhibitory RNA oligonucleotides targeted against the EGFR. Finally, we confirmed that PGF2alpha could potentiate angiogenesis in endometrial adenocarcinoma explants by transactivation of the EGFR and induction of VEGF mRNA expression.

Topics: Adenocarcinoma; Aged; Dinoprost; Endometrial Neoplasms; ErbB Receptors; Female; Humans; MAP Kinase Signaling System; Middle Aged; Neovascularization, Pathologic; Platelet Endothelial Cell Adhesion Molecule-1; Receptors, Prostaglandin; RNA, Messenger; Transcriptional Activation; Tumor Cells, Cultured; Vascular Endothelial Growth Factor A

Prostaglandin F(2 alpha)(PGF(2 alpha)) is a bioactive lipid biosynthesized by cyclooxygenase (COX) enzymes and mediates its biological activity via the heptahelical G(q)-coupled PGF(2 alpha)receptor (FP receptor). This study investigated the expression and molecular signaling of the FP receptor in human endometrial adenocarcinomas. Real-time RT-PCR and Western blot analysis confirmed FP receptor expression in endometrial adenocarcinoma of all grades and differentiation. The expression of FP receptor was up-regulated in all endometrial adenocarcinomas compared with normal endometrium. The site of FP receptor expression was localized by in situ hybridization and immunohistochemistry to the neoplastic epithelial cells in all adenocarcinomas. Treatment of endometrial adenocarcinoma explants with PGF(2 alpha) resulted in mobilization of inositol phosphate signaling, indicating functional FP receptor expression. We investigated whether PGF(2 alpha) could trans-activate the epidermal growth factor receptor (EGFR) and trigger the MAPK signaling pathway. Treatment of adenocarcinoma explants and endometrial adenocarcinoma cells (Ishikawa) with PGF(2 alpha)-phosphorylated EGFR, triggered MAPK signaling and enhanced the proliferation of Ishikawa cells. Inactivation of phospholipase C, EGFR kinase, and MAPK kinase with specific inhibitors abolished PGF(2 alpha)-induced trans-activation of EGFR, MAPK signaling, and Ishikawa cell proliferation. These data suggest that PGF(2 alpha)-FP receptor promote endometrial tumorigenesis via a phospholipase C-mediated phosphorylation of the EGFR and MAPK signaling pathways.

Topics: Adenocarcinoma; Cell Division; Cell Line, Tumor; Culture Techniques; Dinoprost; Endometrial Neoplasms; ErbB Receptors; Female; Humans; Isoenzymes; Mitogen-Activated Protein Kinases; Phospholipase C beta; Receptors, Prostaglandin; Signal Transduction; Tissue Distribution; Type C Phospholipases

The role of individual eicosanoids of the arachidonic acid (AA) cascade in the growth control of A549 human lung adenocarcinoma cells has been studied. Cyclooxygenase and lipoxygenase metabolites of [14C]AA incorporated were actively synthesized in the cultures of tumor cells with full confluence unaccomplished. In such cultures inhibitors of AA metabolism (indomethacin and esculetin) and also a lipoxygenase metabolite of AA, 15-hydroxyeicosatetraenoic acid (15-HETE), significantly suppressed the incorporation of [3H]thymidine and biosynthesis of prostaglandin E2 (PGE2). Other lipoxygenase metabolites of AA (5-HETE and 12-HETE) had no effect on these parameters. The basic fibroblast growth factor (bFGF) had practically no affect on the growth of A549 cells and the PGE2 production in cultures with 5% fetal calf serum (FCS); however, in the presence of 0.5% FCS this factor significantly increased the number of tumor cells. The growth-stimulating effect of bFGF was completely abolished by a cyclooxygenase inhibitor indomethacin. The data suggest a key role of PGE2 in the growth control of A549 cells with an active synthesis of cyclooxygenase and lipoxygenase metabolites of AA, its importance in realization of the mitogenic effect of bFGF, and specific features of 15-HETE as a down-regulator of the PGE2-dependent proliferation.

Topics: Adenocarcinoma; Arachidonic Acids; Carbon Radioisotopes; Cell Division; Cyclooxygenase Inhibitors; Dinoprost; Dinoprostone; DNA; Fibroblast Growth Factor 2; Humans; Hydroxyeicosatetraenoic Acids; Indomethacin; Lung Neoplasms; Thymidine; Tritium; Tumor Cells, Cultured; Umbelliferones

The PC-3 Low Invasive cells and the PC-3 High Invasive cells were used to investigate the correlation of the COX-2 expression and its arachidonic acid metabolites, prostaglandins, with their invasiveness through Matrigel using a Boyden chamber assay. The COX-2 expression in PC-3 High Invasive cells was approximately 3-fold higher than in PC-3 Low Invasive cells while the COX-1 expression was similar in both cell sublines. When incubated with arachidonic acid, PGE2 was the major prostaglandin produced by these cells. PC-3 High Invasive cells produced PGE2 approximately 2.5-fold higher than PC-3 Low Invasive cells. PGD2 was the second most abundant prostaglandin produced by these cells. Both indomethacin (a nonspecific COX inhibitor) and NS-398 (a specific COX-2 inhibitor) inhibited the production of prostaglandins and the cell invasion. PGE2 alone did not induce the cell invasion of PC-3 Low Invasive cells. However, PGE2 reversed the inhibition of cell invasion by NS-398 and enhanced the cell invasion of the PC-3 High Invasive cells. In contrast, PGD2 slightly inhibited the cell invasion. These results suggest that in the PC-3 Low Invasive cells, COX-2-derived PGE2 may not be sufficient to induce cell invasion while in the PC-3 High Invasive cells, PGE2 may be sufficient to act as an enhancer for the cell invasion. Further, PGD2 may represent a weak inhibitor and counteracts the effect of PGE2 in the cell invasion.

Topics: 6-Ketoprostaglandin F1 alpha; Adenocarcinoma; Arachidonic Acid; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Dinoprost; Dinoprostone; Humans; Indomethacin; Isoenzymes; Male; Membrane Proteins; Neoplasm Invasiveness; Nitrobenzenes; Prostaglandin D2; Prostaglandin-Endoperoxide Synthases; Prostaglandins; Prostatic Neoplasms; Sulfonamides; Tumor Cells, Cultured

Several phytochemicals and micronutrients that are present in fruits and vegetables are known to exert cancer chemopreventive effects in several organs, including the colon. Among them, the soybean isoflavonoid genistein received much attention due to its potential anticarcinogenic, antiproliferative effects and its potential role in several signal transduction pathways. The present study was designed to investigate the effect of genistein on azoxymethane (AOM)-induced colon carcinogenesis and to study its modulatory role on the levels of activity of 8-isoprostane, cyclooxygenase (COX), and 15-hydroxyprostaglandin F2alpha dehydrogenase (15-PGDH) in the colonic mucosa and colon tumors of male F344 rats. At 5 weeks of age, groups of male F344 rats were fed control (AIN-76A) diet or a diet containing 250 ppm genistein. Beginning 2 weeks later, all animals except those in the vehicle-treated groups were given weekly s.c. injections of AOM (15 mg/kg body weight) for 2 successive weeks. All rats were continued on their respective dietary regimen for 52 weeks after AOM treatment and were then sacrificed. Colon tumors were evaluated histopathologically. Colonic mucosae and tumors were analyzed for COX, 15-PGDH, and 8-isoprostane levels. Administration of genistein significantly increased noninvasive and total adenocarcinoma multiplicity (P < 0.01) in the colon, compared to the control diet, but it had no effect on the colon adenocarcinoma incidence nor on the multiplicity of invasive adenocarcinoma (P > 0.05). Also, genistein significantly inhibited the 15-PGDH activity (>35%) and levels of 8-iosoprostane (50%) in colonic mucosa and in tumors. In contrast, genistein had no significant effect on the COX synthetic activity, as measured by the rate of formation of prostaglandins and thromboxane B2 from [14C]arachidonic acid. The results of this investigation emphasize that the biological effects of genistein may be organ specific, inhibiting cancer development in some sites yet showing no effect or an enhancing effect on the tumorigenesis at other sites, such as the colon. The inhibition of 8-isoprostane levels by genistein indicates its possible antioxidant potential, which is independent of the observed colon tumor enhancement, yet this agent may also possess several biological effects that overshadow its antioxidant potential. The exact mechanism(s) of colon tumor enhancement by genistein remain to be elucidated; it is likely that its colon tumor-enhancing effect

Topics: Adenocarcinoma; Animals; Anticarcinogenic Agents; Azoxymethane; Carcinogens; Colon; Colonic Neoplasms; Dinoprost; Drug Synergism; F2-Isoprostanes; Genistein; Hydroxyprostaglandin Dehydrogenases; Intestinal Mucosa; Isoflavones; Male; Neoplasms, Experimental; Prostaglandin-Endoperoxide Synthases; Rats; Rats, Inbred F344

Eicosanoids have been implicated in the pathogenesis of cancer and are known to regulate the expression of antigens of the major histocompatibility complex (MHC). In human colon cancer, we have recently observed that: (a) the expression of MHC class I and II antigens are markedly reduced; and (b) the levels of PGE2, but not of PGF2 alpha and LTB4, are elevated compared to histologically normal mucosa. Therefore, we investigated the effect of PGE2, PGF2 alpha and LTB4 on the regulation of MHC class I antigens in two human colon adenocarcinoma cell lines and in a murine model of colon cancer. None of these eicosanoids had any significant effect on the expression of MHC class I antigens in the human colonocytes or the transcription rate of class I genes, with the exception of LTB4 which only modestly suppressed the transcription rate. Similarly, 16, 16-dimethyl-PGE2 had no effect on the expression of MHC class I genes in the colonocytes of BALB/c mice treated with the carcinogen dimethylhydrazine. We conclude that PGE2, PGF2 alpha and LTB4 did not affect the expression of MHC class I antigens in cultured human colon adenocarcinoma cells, and 16, 16-dimethyl PGE2 did not affect their expression in mice, even when mice were treated with a colon carcinogen. Thus, these eicosanoids are an unlikely regulator of the observed underexpression of MHC class I antigens in human colon cancer.

Topics: 16,16-Dimethylprostaglandin E2; Adenocarcinoma; Animals; Colon; Colonic Neoplasms; Dinoprost; Dinoprostone; Eicosanoids; Gene Expression Regulation, Neoplastic; Genes, MHC Class I; Histocompatibility Antigens Class I; Humans; Leukotriene B4; Male; Mice; Mice, Inbred BALB C; Tumor Cells, Cultured

Prostaglandins (PG) have been implicated in the pathogenesis of cancer and play an important role in immune regulation. Colon cancer is associated with elevated levels of PGE2, while aspirin, the prototypical inhibitor of PG synthesis, appears to reduce the incidence of colon cancer by 50%. We have observed that in human colon cancer the expression of HLA class I and II antigens is reduced or lost; loss of HLA antigens is suspected to be a mechanism by which the malignant cell escapes the immune surveillance. We investigated the effect of these eicosanoids on the expression of HLA antigens in human colon adenocarcinoma cell lines. PGE2 down-regulated the expression of the class II antigen HLA-DR in SW1116 cells (65% reduction at 2.8 x 10(-8) M). This effect was dose- and time-dependent, reversible, and specific (PGF2 alpha and LTB4 had no effect; the expression of carcinoembryonic antigen and class I genes were not affected). Aspirin induced the expression of HLA-DR in HT29 cells, a cell line not expressing constitutively HLA-DR. The reduction of HLA-DR by PGE2 was accompanied by reduced messenger RNA (mRNA) levels of HLA-DR alpha and reduced transcription of the corresponding gene. In contrast to HLA-DR, none of these three eicosanoids affected the expression of HLA class I genes, as assessed via determination of protein expression by fluorescence flow cytometric analysis and evaluation of the corresponding class I mRNA levels. We conclude that PGE2 specifically down-regulates the expression of HLA-DR, while it does not affect the expression of class I antigens.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenocarcinoma; Aspirin; Base Sequence; Cell Line; Colonic Neoplasms; Dinoprost; Dinoprostone; DNA Primers; Dose-Response Relationship, Drug; Gene Expression Regulation, Neoplastic; HLA-DR Antigens; Humans; Leukotriene B4; Molecular Sequence Data; Polymerase Chain Reaction; RNA, Messenger; Tumor Cells, Cultured

Topics: Adenocarcinoma; Alkaline Phosphatase; Biological Assay; Dinoprost; Endometrial Neoplasms; Endometrium; Estrogens; Female; Humans; Organ Culture Techniques; Progestins; Tumor Cells, Cultured

Prostaglandins may inhibit or promote tumor cell replication, depending on the cell system that is investigated. In our laboratory, we have established and characterized four different specific human cancer cell lines. The objectives of this study were to examine and compare the prostaglandin endoperoxide synthase (PG synthase, EC 1.14.99.1) activity of these cell lines by measuring the conversion of arachidonate to 3H-PGE2 and 3H-PGF2 alpha. We found that the oral epidermal carcinoma cell line (OEC-M1) had a moderate degree of PG synthase activity. Enzyme activity could be partially blocked (statistically significant) by the addition of epidermal growth factor (EGF) at 20 ng/mL and almost completely inhibited by platelet-derived growth factor at (PDGF) 20 mU/mL. By contrast, we discovered that the human breast adenocarcinoma cell line (BC-M1) did not contain significant PG synthase, and enzyme activity could be significantly activated by the addition of epidermal growth factor at 20 ng/mL and platelet-derived growth factor at 20 mU/mL. We also found that the human stomach adenocarcinoma cell line (SCM-1) had a significant amount of PG synthase activity, and these PG synthase activities were not activated or inhibited by EGF at 20 ng/mL or PDGF at 20 mU/mL. Furthermore, the human fibrosarcoma (FS-M1) cell line also contained a moderate degree of PG synthase activity, which could be significantly inhibited by PDGF at 20 mU/mL but was not inhibited by EGF at 20 ng/mL. The results suggest that EGF and PDGF may be involved in the regulation of the PG synthase activities of human oral, breast, stomach, and fibrosarcoma cancer cells.

Topics: Adenocarcinoma; Breast Neoplasms; Buttocks; Carcinoma, Squamous Cell; Chromatography, Thin Layer; Cyclooxygenase Inhibitors; Dinoprost; Dinoprostone; Enzyme Activation; Epidermal Growth Factor; Female; Fibrosarcoma; Gingival Neoplasms; Humans; Organ Specificity; Platelet-Derived Growth Factor; Prostaglandin-Endoperoxide Synthases; Stomach Neoplasms; Tumor Cells, Cultured

Some of the isoflavonoids present in human diet as well as in urine are expected to exert biologic effects as they have been reported to bind to estrogen receptors and to be estrogenic in other species. This report describes the in vitro assessment of estrogenic effects of isoflavonoids using human endometrial cells and tissue. The relative estrogenic potencies (EC50 values) of estradiol, 3 dietary isoflavonoids (coumestrol, genistein and daidzein) and one of their metabolites (equol), were estimated by using a recently developed multiwell plate in vitro bioassay based on the estrogen-specific enhancement of alkaline phosphatase (AlkP) activity in human endometrial adenocarcinoma cells of the Ishikawa-Var I line. The maximal AlkP activity elicited by the isoflavonoids tested was as high as that achieved with estradiol and their effects were suppressed by the antiestrogens 4-hydroxytamoxifen and ICI 164,384. These results indicate that estradiol and the isoflavonoids exert their effects on AlkP by similar interactions with the estrogen receptor, with potencies depending on binding affinities. The estrogenic effect of equol was confirmed by another in vitro bioassay, based on the estrogen-stimulated enhancement of prostaglandin F2 alpha output by fragments of human secretory endometrium.

Topics: Adenocarcinoma; Alkaline Phosphatase; Biological Assay; Chromans; Coumestrol; Dinoprost; Endometrial Neoplasms; Endometrium; Equol; Estradiol; Female; Genistein; Humans; Isoflavones; Polyunsaturated Alkamides; Tamoxifen; Tumor Cells, Cultured

The intrinsic estrogenic activity of some progestins cannot be properly evaluated by using hormone responsive systems when the chosen end-points are also sensitive to progestagenic activity, usually antagonistic of estrogenic actions. We have therefore applied to the evaluation of some drugs commonly used in contraceptive and hormone replacement formulations a recently developed in vitro method to estimate estrogenic activities, which is based on measurements of the estrogen-stimulated alkaline phosphatase activity in cells of the Ishikawa-Var I human endometrial adenocarcinoma line, a response not influenced by progestins. Whereas progesterone, medroxyprogesterone acetate and danazol were found to be devoid of estrogenic activity in this assay, Org OD-14, norethynodrel, gestrinone (R 2323), norethindrone and dl-norgestrel provoked half maximal increases in alkaline phosphatase activity at concentrations (EC-50) of 7, 14, 140, 200 and 2900 nM, respectively, under conditions in which the corresponding value for estradiol was 8 pM. This intrinsic estrogenic activity can be inhibited by antiestrogens, as verified by reversing the effect of R 2323 with 4-hydroxytamoxifen. Since prostaglandin F2 alpha output by secretory endometrium is increased by estrogens and diminished by progestins, this end-point can serve to evaluate the net effect of drugs with intrinsic estrogenic and progestagenic activities. For instance, R 2323 showed estrogenic activity in this assay whereas Org OD-14 did not. The same in vitro system can be used to evaluate estrogen antagonistic activities of test compounds, using estradiol as the agonist. These in vitro systems are useful in establishing a profile of activities of a drug on a relevant human target tissue, in the screening of synthetic or natural compounds under investigation, and in studies on structure/action relationships.

Topics: Adenocarcinoma; Alkaline Phosphatase; Cell Line; Dinoprost; Endometrial Neoplasms; Estradiol Dehydrogenases; Estrogens; Female; Glycogen; Humans; Kinetics; Progestins; Structure-Activity Relationship

Effects of prostaglandin F2 alpha, E2, D2 and J2 on the DNA and RNA contents of a human endometrial cancer cell lines (SNG and Ishikawa) were studied using flow cytometry. Cytotoxic effects of various prostaglandins on SNG and Ishikawa cell lines were examined and PG J2 and PG D2 were found most active. Among other prostaglandins PG E2 showed a comparable inhibitory activity to cellular growth but PG F2 alpha didn't. In SNG and Ishikawa cell lines after RNase treatment, PG J2, PG D2 and PG E2 caused a decrease of the S-phase and G2 + M-phase cell population in cell cycle. On the other hand, PG F2 alpha caused a increase of the S-phase cell population in cell cycle PG J2, PG D2 and PG E2 after DNase treatment caused a decrease of the relative RNA content in both of cell lines. On the other hand, PG F2 alpha caused a increase of the relative RNA content. It is a noteworthy that PG J2 and PG D2 were remarkably recognized delay of doubling time and decrease of survival fraction under the time and dose dependence. These effects occur not only by direct lethal influence of the prostaglandins, but also by substantially inhibit RNA and DNA synthesis with a delay of the cell cycle. These results might be suggested a role for prostaglandin J2 and D2 in the regulation of growth of endometrial adenocarcinoma cells.

Topics: Adenocarcinoma; Cell Cycle; Cell Division; Cells, Cultured; Colony-Forming Units Assay; Dinoprost; Dinoprostone; Female; Flow Cytometry; Humans; Prostaglandin D2; Prostaglandins D; Prostaglandins E; Prostaglandins F; Tumor Stem Cell Assay; Uterine Neoplasms

Massive secretory diarrhea is associated with some villous adenomas. The mechanism of this secretion is unknown but the character of the diarrhea resembles that of cyclic nucleotide-mediated diarrheas. We have compared the cyclic nucleotide metabolism of a large secretory villous adenoma with a nonsecretory villous adenoma, a solid carcinoma and their normal mucosae. The adenylate cyclase, cyclic AMP content, and a cyclic AMP-dependent protein kinase ratios in the secretory tumor were increased as compared to these values in the nonsecretory tumors and normal mucosae, a situation similar to that seen with cholera toxin-induced diarrhea. Our data suggest that the massive diarrhea in our patient with a secretory villous adenoma may be related to increased adenylate cyclase activity.

Topics: Adenocarcinoma; Adenoma; Adenylyl Cyclases; Aged; Cyclic AMP; Diarrhea; Dinoprost; Dinoprostone; Female; Humans; Intestinal Mucosa; Intestinal Neoplasms; Male; Middle Aged; Nucleotides, Cyclic; Paraneoplastic Endocrine Syndromes; Prostaglandins E; Prostaglandins F; Protein Kinases; Sigmoid Neoplasms

Tissue contents of prostaglandins (PG) PGE2, PGE2a and 6-keto-PGF1a (degradation product of PGI2) were determined in specimens of advanced human ovarian cancer (n = 11). The PG levels (ng/mg tissue protein) varied widley: PGE2 17-515; PGF2a 2-43 and 6-keto-PGF1a 5-105. Tumors of patients without response to chemotherapy contained more PGE2, PGF2a and 6-keto-PGF1a than did tumors responding to chemotherapy. PG production was investigated in two ovarian carcinoma-derived cell lines. The ability of these cells to synthesize PG varied depending on the cell density. An increase of cell number was associated with a decrease of PG yield. PG formation was inhibited by indomethacin in a concentration-dependent manner. The present study suggests that ovarian carcinoma cells form PG in vivo and vitro.

Topics: 6-Ketoprostaglandin F1 alpha; Adenocarcinoma; Animals; Cell Line; Dinoprost; Dinoprostone; Female; Humans; Mice; Mice, Nude; Ovarian Neoplasms; Prostaglandins; Prostaglandins E; Prostaglandins F

Enhanced production of prostaglandins (PGs) by experimentally-induced and naturally occurring tumors and their effect on tumor growth and immunosurveillance have been noted. Directed toward further evaluation of the relationship between prostatic tumor growth and its milieu, i.e., microenvironment, we investigated the possible correlation between levels of PGs, tumor size, and metastatic potential. For this purpose, the levels of PGE2 and PGF2 alpha in plasma and tumor effusions of three tumor sublines of the Dunning R-3327 rat prostate adenocarcinoma were measured: R-3327H, well-differentiated, slow-growing, and poorly metastatic; R-3327G, poorly differentiated, fast-growing, and poorly metastatic; and R-3327 Mat LyLu, anaplastic, fast-growing, and highly metastatic. The level of PGF2 alpha was highly variable with no significant differences being noted between the tumor sublines. The mean values of PGF2 alpha were, however, higher, although not significantly so, in the smaller tumors within each of the sublines. The levels of PGE2 were significantly higher in Mat LyLu effusions than those from the nonmetastasizing R-3327G and H sublines. Evaluation and comparison of the relationship between tumor burden, i.e., size versus levels of PGE2 and PGF2 alpha showed no significant differences. A vasodilator and regulator of immunological responsiveness, PGE2, may function as a modulator of tumor metastases. In consonance with studies by others elevated levels of PGE2 may possibly serve as a prognostic marker for the high metastatic potential of neoplastic cells.

Topics: Adenocarcinoma; Androgens; Animals; Dinoprost; Dinoprostone; Immunologic Surveillance; Male; Neoplasm Metastasis; Neoplasm Transplantation; Neoplasms, Hormone-Dependent; Prostaglandins E; Prostaglandins F; Prostatic Neoplasms; Rats

A comparison of tissue concentrations and biosynthesis of prostaglandin (PG)E2, PGF2 alpha, 6-keto-PGF1 alpha (degradation production of PGI2) and thromboxane (TX)B2 (degradation product of TXA2) was made in normal mammary glands obtained from virgin female Sprague-Dawley rats and in N-nitrosomethylurea (NMU)-induced mammary adenocarcinomas. The tissue concentrations (ng/g wet weight) of all 4 compounds were significantly higher in the NMU-induced tumor than in normal mammary tissue: PGE2, 210 +/- 37 vs 25 +/- 6; PGF2 alpha, 287 +/- 48 vs 23 +/- 8; 6-keto-PGF1 alpha, 294 +/- 42 vs 31 +/- 8; and TXB2, 260 +/- 49 vs 27 +/- 5 (mean +/- S.E.M.). Microsomal prostaglandin synthetase activity in NMU-induced tumors was also significantly higher than in normal tissue for all but 6-keto-PGF1 alpha: PGE2, 226 +/- 16 vs 50 +/- 9; PGF2 alpha, 28 +/- 3 vs 4 +/- 1; 6-keto-PGF1 alpha, 14 +/- 2 vs 11 +/- 2; and TXB2, 17 +/- 1 vs 10 +/- 1 ng/mg protein (mean +/- S.E.M.). There was no apparent relationship between either tumor size or age and the ability of microsomal enzyme to synthesize prostaglandins, although the content of prostaglandins extracted from tumor tissue was inversely related to the tumor size.

Topics: 6-Ketoprostaglandin F1 alpha; Adenocarcinoma; Animals; Dinoprost; Dinoprostone; Female; Mammary Glands, Animal; Mammary Neoplasms, Experimental; Methylnitrosourea; Microsomes; Prostaglandin-Endoperoxide Synthases; Prostaglandins; Prostaglandins E; Prostaglandins F; Rats; Rats, Inbred Strains; Thromboxane B2

The regulation of murine mammary tumor virus (MuMTV) production by mammotropic hormones, hormonomimetic substances, and cyclic nucleotides was investigated. The virus produced in control and treated mammary tumor cell cultures was quantitated by measuring the supernatant reverse transcriptase activity in exogenous reaction using poly(rC).oligo(dG) as template-primer. Two days after exposure, the synthetic glucocorticoid, dexamethasone (DXMT), increased spontaneous MuMTV production at optimal concentration (0.1 mumol) up to ten times. Dibutyryl derivative of cyclic AMP had no effect on spontaneous MuMTV production, whereas the drug potentiated suboptimal concentrations of the glucocorticoid. Natural prostaglandins, potent agonists of adenylate cyclase catalyzing intracellular synthesis of cyclic AMP, enhanced both basal (up to five times) and DXMT-stimulated (up to 1.6 times) MuMTV replication. The MuMTV-stimulating activity of prostaglandins decreased in the order of PGA1 greater than PGE1 greater than PGB1 greater than PGF2 alpha. Prostaglandins can be replaced partially by norepinephrine and isoproterenol by enhancing the DXMT-mediated MuMTV stimulation, whereas these drugs remained without effect on spontaneous MuMTV production. Theophylline, an antagonist of cAMP-phosphodiesterase converting cAMP to AMP, enhanced the virus-stimulating activity of DXMT as well as of prostaglandins. The enhancement of MuMTV production by adenylate cyclase agonists do not correlate absolutely with the estimates of intracellular cAMP levels, since the highest amounts of cAMP has been repeatedly observed in cells treated with PGE1 and norepinephrine. The results indicate that besides hormones, other hormone-like substances and cyclic nucleotides may be involved in the complex mechanism of hormone-regulated MuMTV genome expression.

Topics: Adenocarcinoma; Adenylyl Cyclases; Alprostadil; Animals; Cell Line; Cyclic AMP; Dexamethasone; Dinoprost; Female; Mammary Neoplasms, Experimental; Mammary Tumor Virus, Mouse; Mice; Mice, Inbred C3H; Prostaglandins; Prostaglandins A; Prostaglandins B; Prostaglandins E; Prostaglandins F; Virus Replication

13,14-Dihydro-15-keto-prostaglandin F2 alpha (13,14-DHK-PGF2 alpha) represents a stable product of degradation after pulmonary flow and it is shown to be reliably measured by radioimmunoassay. In patients with urogenital tumors, serum levels of 13,14-DHK-PGF2 alpha are distinctly elevated when compared to a control group. The rate of synthesis of this compound in urogenital tumors, however, appears to be different.

Topics: Adenocarcinoma; Dinoprost; Female; Humans; Kidney Neoplasms; Male; Neoplasms, Germ Cell and Embryonal; Prostaglandins F; Prostatic Hyperplasia; Prostatic Neoplasms; Radioimmunoassay; Testicular Neoplasms; Urinary Bladder Neoplasms; Urogenital Neoplasms