guanosine-triphosphate and Carcinoma

With over 100 members in humans, the Ras superfamily is a diverse group of monomeric G proteins participating in many cellular processes. Members of the Ras, Rho, and Arf families have been shown to regulate cell motility in fibroblasts and epithelial cells. Ras and Rho family members are also widely involved in human tumorigenesis, either through activating mutations or by overexpression. In this review, tools for studying carcinoma cell migration are discussed and evidence for regulation of carcinoma cell motility by specific Ras superfamily members is summarized. Novel emerging mechanisms of migration in carcinoma cells involving RhoC and Ral are also discussed.

Topics: ADP-Ribosylation Factors; Carcinoma; Cell Movement; Enzyme Activation; Genes, ras; Guanosine Triphosphate; Humans; Monomeric GTP-Binding Proteins; Multigene Family; Mutation; Neoplasm Invasiveness; Neoplasm Proteins; rab GTP-Binding Proteins; ras Proteins; rho GTP-Binding Proteins

Preeclampsia is characterized by maternal hypertension and multi-organ injury. Elongation factor Tu GTP binding domain containing 2 (EFTUD 2) and the Pregnancy Zone Protein (PZP) seem to be important immunomodulatory factors in early gestation. Little is known about the role of EFTUD2 and PZP in disorders of late pregnancy like preeclampsia, HELLP syndrome and intrauterine growth restriction (IUGR). PZP, EFTUD2 and hCG expression was investigated by immunohistochemistry in the placenta of healthy pregnancies (n = 13), preeclampsia (n = 11), HELLP syndrome (n = 12) and IUGR (n = 8). Correlation analysis of protein expression was performed via Spearman correlation coefficient. The characterization of EFTUD2 and PZP expressing cells was evaluated by double-immunofluorescence. After cultivation of the chorion carcinoma cell line BeWo with hCG the expression of PZP and EFTUD2 was investigated by immunocytochemistry. PZP expression was significantly downregulated in the syncytiotrophoblast (ST) and extravillous trophoblast (EVT) of preeclampsia (ST: p 0.001, EVT:p = 0.019) and HELLP syndrome (ST: p = 0.004, EVT: p = 0.035). The expression of EFTUD2 was significantly lower in preeclampsia (ST: p = 0.003, EVT: p 0.001), HELLP syndrome (ST: p = 0.021, EVT: = 0.001, EVT: p = 0.001). EVTs were identified as EFTUD2 and PZP expressing cells by double-immunofluorescence. Stimulation of BeWo chorion carcinoma cells with hCG 1000 IU/mL for 48 h resulted in a significant upregulation of PZP expression (p = 0.027). Our results indicate that PZP and EFTUD2 might be involved in the development of placental dysfunction in preeclampsia and HELLP syndrome.

Topics: Carcinoma; Female; Fetal Growth Retardation; Guanosine Triphosphate; HELLP Syndrome; Humans; Peptide Elongation Factor Tu; Peptide Elongation Factors; Placenta; Pre-Eclampsia; Pregnancy; Pregnancy Proteins; Ribonucleoprotein, U5 Small Nuclear

Protein kinase C (PKC) ε, a key signaling transducer implicated in mitogenesis, survival, and cancer progression, is overexpressed in human primary non-small cell lung cancer (NSCLC). The role of PKCε in lung cancer metastasis has not yet been established.. Here we show that RNAi-mediated knockdown of PKCε in H358, H1299, H322, and A549 NSCLC impairs activation of the small GTPase Rac1 in response to phorbol 12-myristate 13-acetate (PMA), serum, or epidermal growth factor (EGF). PKCε depletion markedly impaired the ability of NSCLC cells to form membrane ruffles and migrate. Similar results were observed by pharmacological inhibition of PKCε with εV1-2, a specific PKCε inhibitor. PKCε was also required for invasiveness of NSCLC cells and modulated the secretion of extracellular matrix proteases and protease inhibitors. Finally, we found that PKCε-depleted NSCLC cells fail to disseminate to lungs in a mouse model of metastasis.. Our results implicate PKCε as a key mediator of Rac signaling and motility of lung cancer cells, highlighting its potential as a therapeutic target.

Topics: Animals; Carcinoma; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Cell Movement; Disease Progression; Enzyme Activation; Extracellular Matrix; Gene Expression Regulation, Neoplastic; Guanosine Triphosphate; Humans; Lung Neoplasms; Male; Mice; Mice, Nude; Neoplasm Metastasis; Protein Kinase C-epsilon; rac GTP-Binding Proteins; RNA Interference; Signal Transduction

While a significant amount is known about the biochemical signaling pathways of the Rho family GTPase Cdc42, a better understanding of how these signaling networks are coordinated in cells is required. In particular, the predominant subcellular sites where GTP-bound Cdc42 binds to its effectors, such as p21-activated kinase 1 (PAK1) and N-WASP, a homolog of the Wiskott-Aldritch syndrome protein, are still undetermined. Recent fluorescence resonance energy transfer (FRET) imaging experiments using activity biosensors show inconsistencies between the site of local activity of PAK1 or N-WASP and the formation of specific membrane protrusion structures in the cell periphery. The data presented here demonstrate the localization of interactions by using multiphoton time-domain fluorescence lifetime imaging microscopy (FLIM). Our data here establish that activated Cdc42 interacts with PAK1 in a nucleotide-dependent manner in the cell periphery, leading to Thr-423 phosphorylation of PAK1, particularly along the lengths of cell protrusion structures. In contrast, the majority of GFP-N-WASP undergoing FRET with Cy3-Cdc42 is localized within a transferrin receptor- and Rab11-positive endosomal compartment in breast carcinoma cells. These data reveal for the first time distinct spatial association patterns between Cdc42 and its key effector proteins controlling cytoskeletal remodeling.

Topics: Binding Sites; Breast Neoplasms; Carcinoma; cdc42 GTP-Binding Protein; Cell Cycle Proteins; Cell Line, Tumor; Cell Membrane; Clathrin-Coated Vesicles; Endosomes; Fluorescence Resonance Energy Transfer; Green Fluorescent Proteins; Guanine Nucleotide Exchange Factors; Guanosine Triphosphate; Humans; Nerve Tissue Proteins; p21-Activated Kinases; Phosphorylation; Protein Serine-Threonine Kinases; Rho Guanine Nucleotide Exchange Factors; Wiskott-Aldrich Syndrome Protein, Neuronal

Signalling by integrin-mediated cell anchorage to extracellular matrix proteins is co-operative with other receptor-mediated signalling pathways to regulate cell adhesion, spreading, proliferation, survival, migration, differentiation and gene expression. It was observed that an anchorage-independent gastric carcinoma cell line (SNU16) became adherent on TGF-beta1 (transforming growth factor beta1) treatment. To understand how a signal cross-talk between integrin and TGF-beta1 pathways forms the basis for TGF-beta1 effects, cell adhesion and signalling activities were studied using an adherent subline (SNU16Ad, an adherent variant cell line derived from SNU16) derived from the SNU16 cells. SNU16 and SNU16Ad cells, but not integrin alpha5-expressing SNU16 cells, showed an increase in adhesion on extracellular matrix proteins after TGF-beta1 treatment. This increase was shown to be mediated by an integrin alpha3 subunit, which was up-regulated in adherent SNU16Ad cells and in TGF-beta1-treated SNU16 cells, compared with the parental SNU16 cells. After TGF-beta1 treatment of SNU16Ad cells on fibronectin, Tyr-416 phosphorylation of c-Src was increased, but Ras-GTP loading and ERK1/ERK2 (extracellular-signal-regulated kinases 1 and 2) activity were decreased, which showed a dependence on c-Src family kinase activity. Studies on adhesion and signalling activities using pharmacological inhibitors or by transient-transfection approaches showed that inhibition of ERK1/ERK2 activity increased TGF-beta1-mediated cell adhesion slightly, but not the basal cell adhesion significantly, and that c-Src family kinase activity and decrease in Ras/ERKs cascade activity were required for the TGF-beta1 effects. Altogether, the present study indicates that TGF-beta1 treatment causes anchorage-independent gastric carcinoma cells to adhere by an increase in integrin alpha3 level and a c-Src family kinase activity-dependent decrease in Ras/ERKs cascade activity.

Topics: Animals; Carcinoma; Cell Adhesion; Culture Media, Serum-Free; DNA Methylation; Enzyme Inhibitors; Extracellular Matrix; Fibronectins; Gene Expression Regulation, Neoplastic; Guanosine Triphosphate; Humans; Integrin alpha3; Integrins; MAP Kinase Signaling System; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinases; Neoplasm Proteins; Phosphatidylinositol 3-Kinases; Protein Subunits; ras GTPase-Activating Proteins; Rats; src-Family Kinases; Stomach Neoplasms; Transforming Growth Factor beta; Transforming Growth Factor beta1

Animal, epidemiological and clinical studies have demonstrated the anti-tumor activity of pharmacological proteasome inhibitors and the cancer-preventive effects of green tea consumption. Previously, one of our laboratories reported that natural ester bond-containing green tea polyphenols (GTPs), such as (-)-epigallocatechin-3-gallate [(-)-EGCG] and (-)-gallocatechin-3-gallate [(-)-GCG], are potent and specific proteasome inhibitors. Another of our groups, for the first time, was able to enantioselectively synthesize (-)-EGCG as well as other analogs of this natural GTP. Our interest in designing and developing novel synthetic GTPs as proteasome inhibitors and potential cancer-preventive agents prompted our current study.. GTP analogs, (+)-EGCG, (+)-GCG, and a fully benzyl-protected (+)-EGCG [Bn-(+)-EGCG], were prepared by enantioselective synthesis. Inhibition of the proteasome or calpain (as a control) activities under cell-free conditions were measured by fluorogenic substrate assay. Inhibition of intact tumor cell proteasome activity was measured by accumulation of some proteasome target proteins (p27, I kappa B-alpha and Bax) using Western blot analysis. Inhibition of tumor cell proliferation and induction of apoptosis by synthetic GTPs were determined by G(1) arrest and caspase activation, respectively. Finally, inhibition of the transforming activity of human prostate cancer cells by synthetic GTPs was measured by a colony formation assay.. (+)-EGCG and (+)-GCG potently and specifically inhibit the chymotrypsin-like activity of purified 20S proteasome and the 26S proteasome in tumor cell lysates, while Bn-(+)-EGCG does not. Treatment of leukemic Jurkat T or prostate cancer LNCaP cells with either (+)-EGCG or (+)-GCG accumulated p27 and IkappaB-alpha proteins, associated with an increased G(1) population. (+)-EGCG treatment also accumulated the pro-apoptotic Bax protein and induced apoptosis in LNCaP cells expressing high basal levels of Bax, but not prostate cancer DU-145 cells with low Bax expression. Finally, synthetic GTPs significantly inhibited colony formation by LNCaP cancer cells.. Enantiomeric analogs of natural GTPs, (+)-EGCG and (+)-GCG, are able to potently and specifically inhibit the proteasome both, in vitro and in vivo, while protection of the hydroxyl groups on (+)-EGCG renders the compound completely inactive.

Topics: Adenocarcinoma; Apoptosis; bcl-2-Associated X Protein; Calpain; Carcinoma; Carrier Proteins; Caspases; Cell Line; Cysteine Endopeptidases; G1 Phase; Guanosine Triphosphate; Humans; Intracellular Signaling Peptides and Proteins; Jurkat Cells; Male; Microfilament Proteins; Multienzyme Complexes; Muscle Proteins; Phenols; Polymers; Prostatic Neoplasms; Proteasome Endopeptidase Complex; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-bcl-2; Stereoisomerism; Tea; Transcriptional Elongation Factors

Codon 12 mutations are frequent in the Ki-ras oncogene in human lung adenocarcinomas, but the effects of these alterations have not been well characterized in lung epithelial cells. Murine primary lung tumors derived from peripheral epithelial cells also may present Ki-ras mutations and are useful models for study of early phases of tumor development. One hypothesis is that Ki-ras mutation and/or a Ki-ras p21 increase could enhance Ki-ras p21-GTP and cell-cycle stimulation through raf-1 and extracellularly regulated protein kinases (Erks). We examined lung tumors 1-7 mm in largest dimension initiated in male Swiss mice by N-nitrosodimethylamine for pathologic type, Ki-ras mutations and levels of total Ki-ras p21, Ki-ras p21 bound to GTP, raf-1, Erk1 and Erk2 and their phosphorylated (activated) forms, and proliferating cell nuclear antigen. Total Ki-ras p21 and activated ras-GTP were not significantly greater in tumors than in normal lung or in tumors with versus those without Ki-ras mutations. Carcinomas with Ki-ras mutations were significantly smaller than those without mutations. Carcinomas were significantly larger than adenomas only for tumors without mutations. High levels of Erk2 and correlation of Erk2 amount with ras-GTP were specific characteristics of tumors with Ki-ras mutations. Size of all tumors correlated with ras-GTP but not with proliferating cell nuclear antigen. Raf-1 was expressed mainly in alveolar macrophages in normal lung but was focally upregulated in papillary areas of some tumors. The results indicate that Ki-ras influences the characteristics of lung tumors, but a linear ras-raf-Erk-cell-cycle control sequence does not adequately characterize tumorigenic events in this model. Mol. Carcinog. 28:156-167, 2000.

Topics: Adenoma; Animals; Apoptosis; Carcinoma; Cell Cycle; Cell Transformation, Neoplastic; Codon; Dimethylnitrosamine; DNA Mutational Analysis; DNA, Neoplasm; Genes, ras; Guanosine Triphosphate; Humans; Lung Neoplasms; Male; Mice; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinases; Neoplasm Proteins; Proliferating Cell Nuclear Antigen; Proto-Oncogene Proteins c-raf; Proto-Oncogene Proteins p21(ras); Species Specificity

The molecular mechanisms by which ovarian hormones stimulate growth of breast tumors are unclear. It has been reported previously that estrogens activate the signal-transducing Src/p21(ras)/Erk pathway in human breast cancer cells via an interaction of estrogen receptor (ER) with c-Src. We now show that progestins stimulate human breast cancer T47D cell proliferation and induce a similar rapid and transient activation of the pathway which, surprisingly, is blocked not only by anti-progestins but also by anti-estrogens. In Cos-7 cells transfected with the B isoform of progesterone receptor (PRB), progestin activation of the MAP kinase pathway depends on co-transfection of ER. A transcriptionally inactive PRB mutant also activates the signaling pathway, demonstrating that this activity is independent of transcriptional effects. PRB does not interact with c-Src but associates via the N-terminal 168 amino acids with ER. This association is required for the signaling pathway activation by progestins. We propose that ER transmits to the Src/p21(ras)/Erk pathway signals received from the agonist-activated PRB. These findings reveal a hitherto unrecognized cross-talk between ovarian hormones which could be crucial for their growth-promoting effects on cancer cells.

Topics: Animals; Breast Neoplasms; Carcinoma; COS Cells; CSK Tyrosine-Protein Kinase; Enzyme Activation; Enzyme Inhibitors; Epidermal Growth Factor; Estradiol; Gene Expression Regulation; Guanosine Triphosphate; Hormone Antagonists; Humans; Mitogen-Activated Protein Kinase 1; Point Mutation; Promegestone; Protein-Tyrosine Kinases; Proto-Oncogene Proteins p21(ras); Receptors, Estrogen; Receptors, Progesterone; Signal Transduction; src-Family Kinases; Tamoxifen; Transcriptional Activation; Tumor Cells, Cultured

The activation status of the ras pathway was studied in eight ovarian tumor cell lines. Three biochemical parameters indicative of ras activation were tested: (a) the ratio of the ras-GTP:ras-GDP complex; (b) the activity of mitogen-activated protein kinases p42/p44; and (c) ets-2 phosphorylation at position threonine 72, a mitogen-activated protein kinase phosphorylation site in vivo. Four of the ovarian tumor cell lines had an activated ras pathway by these three parameters, whereas only one of these contained a mutated ras gene. In addition, ras/ets-2 responsive genes such as the urokinase plasminogen activator (uPA) were activated in these four cell lines. Transient transfection assays indicated that the compound ets-AP1 oncogene responsive enhancer present in the uPA gene was the target of ras signaling in ovarian tumor cells and that the combination of activated ras and ets-2 could superactivate the uPA enhancer element. Coexpression of the dominant-negative ras-Asn17 cDNA gene abrogated activity of this uPA element in ovarian tumor cells. These data indicate that ets-2 is a nuclear target of ras action in ovarian tumor cell lines and that ras signaling pathways may be activated in ovarian cancer by mechanisms independent of direct genetic damage to ras genes.

Topics: Antineoplastic Agents; Calcium-Calmodulin-Dependent Protein Kinases; Carcinoma; DNA-Binding Proteins; Enzyme Activation; Female; Gene Expression Regulation; Genes, ras; Genistein; Guanosine Triphosphate; Humans; Ovarian Neoplasms; Phosphorylation; Proto-Oncogene Protein c-ets-2; Proto-Oncogene Proteins; Repressor Proteins; Trans-Activators; Transcription Factors; Tumor Cells, Cultured; Urokinase-Type Plasminogen Activator

Topics: Antineoplastic Agents; Carcinoma; Cell Division; Cell Movement; Chemoprevention; Computer-Aided Design; Coumarins; Drug Design; Guanine; Guanosine Triphosphate; Humans; Molecular Structure; Point Mutation; Protein Binding; Proto-Oncogene Proteins p21(ras); Structure-Activity Relationship; Tumor Cells, Cultured; Umbelliferones; Urinary Bladder Neoplasms

The role of G protein mutations in the pathogenesis of adrenal cortex neoplasms is controversial. Two published studies disagree on the existence of a cysteine or histidine for arginine substitution at position 179 (R179C/H) of the GTP binding region of the alpha chain of an inhibitory G protein (Gi2alpha) in these tumors. Prior studies using detection by mutation-specific oligonucleotide hybridization showed either 3 of 11 or 0 of 56 tumors harbored mutations. To resolve this discrepancy and ascertain the importance of the R179C/H Gi2alpha mutation in the development of adrenal cortex tumors, we screened tumors from 29 patients (24 with adenoma, 5 with carcinoma) using a more sensitive assay employing polymerase chain reaction (PCR) and examination for restriction fragment length polymorphisms (RFLP). Detection of the potential R179C/H mutation by this technique was possible because the wild-type coding sequence includes the BSTU-1 restriction endonuclease recognition site CGCG, whereas the mutated gene does not. Results showed complete digestion of the amplified DNA samples from all 29 patients and the negative control DNA by BSTU-1, indicating that all tumor samples exhibited only the wild-type sequence. Direct sequencing of PCR product from four tumor samples confirmed the presence of only the wild-type sequence. The 0 of 29 rate of R179C/H mutations we found in Gi2alpha is different than the 3 of 11 positive rate (p < 0.05, Fishers' exact) previously reported but agrees with the report showing 0 of 56 mutations. We conclude a mutation at position 179 of Gi2alpha is not important in the pathogenesis of most adrenal cortical tumors.

Topics: Adenoma; Adrenal Cortex Neoplasms; Arginine; Base Sequence; Carcinoma; Codon; Cysteine; DNA Restriction Enzymes; GTP-Binding Protein alpha Subunits, Gi-Go; GTP-Binding Proteins; Guanosine Triphosphate; Histidine; Humans; Molecular Sequence Data; Oncogenes; Point Mutation; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length

EF-1C is a component of the aggregate EF-1B, consisting of the subunit forms EF-1A.EF-1C; it was isolated by dissociation of this aggregate in the presence of GTP. The subunit form EF-1C stimulates binding of aminoacyl-tRNA to ribosomes, catalysed by EF-1A, similarly as EF-1 beta gamma which stimulates the activity of EF-1 in other eukaryotic cells. EF-1C in the presence of 6 M urea was separated into two polypeptides. Polypeptide of molecular mass 32,000 Da is responsible for regeneration of the EF-1A.GTP active complex. Thermal sensitivity of EF-1A was much higher than that of EF-1B, thus a protective role of EF-1C in the EF-1A.EF-1C complex is suggested.

Topics: Animals; Carcinoma; Electrophoresis, Polyacrylamide Gel; Guanosine Diphosphate; Guanosine Triphosphate; Liver; Macromolecular Substances; Neoplasm Proteins; Neoplasms, Experimental; Peptide Biosynthesis; Peptide Elongation Factor 1; Peptide Elongation Factors; Peptides; Rats; Ribosomes; RNA, Transfer, Phe; Stimulation, Chemical; Tumor Cells, Cultured

Since taxol (NSC 125975) and tiazofurin (NSC 286193) attack at two different sites in microtubular synthetic processes, we tested the rationale that the two drugs might be synergistic in human ovarian (OVCAR-5), pancreatic (PANC-1) and lung carcinoma (H-125) cells and in rat hepatoma 3924A cells. In human OVCAR-5, PANC-1, H-125 and rat 3924A cells, for taxol the anti-proliferative IC50 was 0.05, 0.06, 0.03 and 0.04 microM, respectively; for tiazofurin IC50 = 8.3, 2.3, 1.8 and 6.9 microM. Thus, the concentrations for taxol required for IC50 for inhibiting cell proliferation were 166-, 38-, 60- and 173-fold lower than those for tiazofurin. Taxol and tiazofurin proved synergistic in all four cell lines tested. The synergism of taxol with tiazofurin should have implications in the clinical treatment of human solid tumors with particular relevance to ovarian, pancreatic, lung and hepatocellular carcinomas.

Topics: Animals; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Carcinoma; Carcinoma, Adenosquamous; Cell Division; Drug Screening Assays, Antitumor; Drug Synergism; Female; Guanosine Diphosphate; Guanosine Triphosphate; Humans; Liver Neoplasms, Experimental; Lung Neoplasms; Ovarian Neoplasms; Paclitaxel; Pancreatic Neoplasms; Rats; Ribavirin; Spindle Apparatus; Tumor Cells, Cultured

The present investigation was performed in order to study the properties of abnormal membrane function related to ACTH receptor-adenylate cyclase system interaction in human ACTH-unresponsive adrenocortical cancer. Two tissues of adrenocortical cancer obtained from a patient with Cushing's syndrome (CS) and a case presenting no abnormal endocrinological findings (NF) were used for in vitro studies, comparing with three normal adrenal tissues. The addition of ACTH alone and ACTH plus 10(-6) M GppNHp did not enhance the adenylate cyclase (AC) activity in the CS and NF tissues. Relative insensitivity of AC to GTP, GppNHp, and cholera toxin was observed for the NF tissue, while the rate of response to GppNHp for the CS tissue which also showed relative insensitivity to GTP and cholera toxin was similar to that for the normal tissues. Forskolin which is reported to directly activate the catalytic unit of the AC complex increased the AC activity of both CS and NF tissues as well as that of the normal tissues. Therefore, the function of the catalytic unit itself may be rather well preserved in these tumor tissues. These results suggest that the lack of ACTH receptor at the cell membrane surface might be responsible for ACTH-unresponsiveness in the CS tissue, although an accelerated degradation of GTP could contribute to decreased activity of GTP-binding protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenylyl Cyclases; Adrenal Cortex Neoplasms; Adrenocorticotropic Hormone; Carcinoma; Cell Membrane; Cholera Toxin; Colforsin; GTP-Binding Proteins; Guanosine Triphosphate; Guanylyl Imidodiphosphate; Humans; Receptors, Corticotropin; Receptors, Pituitary Hormone

The action of thyrotropin (TSH) on plasma membranes was studied to elucidate the mechanism of hormonal regulation of malignant versus normal human thyroid tissue. Thyroid plasma membranes of six specimens of papillary or follicular carcinoma and six of adenoma, as well as adjacent normal tissue obtained from these patients, were evaluated with respect to binding of 125I-labeled TSH and stimulation of adenylate cyclase. Scatchard analysis of TSH binding revealed the presence of two species of binding sites in normal thyroid of different affinities and capacities. In 11 of 12 tumors studied, the high-affinity binding site remained intact; however, the total number of low-affinity sites was markedly lower than normal tissue. Other parameters of binding were not altered in neoplastic thyroid. In each of these tissues, the hormone responsiveness and kinetics of adenylate cyclase activation were essentially identical to those observed in normal tissue, although basal activity was typically greater in the neoplasm. One carcinoma was totally deficient in both 125I-labeled TSH binding and TSH-stimulatable adenylate cyclase, although basal activity was detected. Furthermore, adenylate cyclase of this specimen was not activated by prostaglandin, in contrast to normal thyroid and other thyroid tumors. These results suggest that: (a) clinical behavior of thyroid carcinomas may not be reflected by TSH receptor-adenylate cyclase function; (b) lack of clinical response as manifest by tumor regression cannot be ascribed to the absence of functional TSH receptors or adenylate cyclase; and (c) decreased low-affinity binding present in tumors is not correlated with altered hormone responsiveness of adenylate cyclase but may reflect more general cancer-induced changes in membrane structure or composition.

Topics: Adenoma; Adenylyl Cyclases; Carcinoma; Cell Membrane; Enzyme Activation; Guanosine Triphosphate; Humans; Receptors, Cell Surface; Sodium Fluoride; Thyroid Neoplasms; Thyrotropin

Topics: Adenosine Triphosphate; Animals; Carcinoma; Cell Nucleolus; Cells, Cultured; Dactinomycin; DNA-Directed RNA Polymerases; Guanine; Guanosine Triphosphate; HeLa Cells; Humans; Mouth Neoplasms; RNA, Neoplasm; RNA, Ribosomal; Tritium; Uridine

Topics: Base Sequence; Carcinoma; Cell Line; Chromatography, Gel; DNA-Directed RNA Polymerases; Guanosine Triphosphate; Humans; Isoenzymes; Mouth Neoplasms; Phosphorus Radioisotopes; RNA; Transcription, Genetic