cyclin-d1 and Prostatic-Hyperplasia

Metabolic syndrome (MetS) is a combination of metabolic disorders that can predispose individuals to benign prostatic hyperplasia (BPH). The inhibition of the cannabinoid 1 (CB1) receptor has been used to treat metabolic disorders in animal models. This study reports the use of a peripherally restricted CB1 antagonist (AM6545) and a neutral CB1 antagonist (AM4113) to improve MetS-related BPH in rats. Animals were divided into three control groups to receive either a normal rodent diet, AM6545, or AM4113. MetS was induced in the fourth, fifth, and sixth groups using a concentrated fructose solution and high-salt diet delivered as food pellets for eight weeks. The fifth and sixth groups were further given AM6545 or AM4113 for additional four weeks. Body and prostate weights were measured and prostate sections were stained with hematoxylin eosin. Cyclin D1, markers of oxidative stress and inflammation, and levels of the endocannabinoids were recorded. BPH in rats with MetS was confirmed through increased prostate weight and index, as well as histopathology. Treatment with either AM6545 or AM4113 significantly decreased prostate weight, improved prostate histology, and reduced cyclin D1 expression compared with the MetS group. Groups treated with CB1 antagonists experienced reduced lipid peroxidation, recovered glutathione depletion, restored catalase activity, and had lower inflammatory markers interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α). MetS rats treated with either AM6545 or AM4113 showed reduced concentrations of anandamide (AEA) and 2-arachidonoylglycerol (2-AG) in the prostate compared with the MetS group. In conclusion, the CB1 antagonists AM6545 and AM4113 protect against MetS-induced BPH through their anti-proliferative, antioxidant, and anti-inflammatory effects.

Topics: Animals; Cannabinoid Receptor Antagonists; Cyclin D1; Humans; Male; Metabolic Syndrome; Piperidines; Prostatic Hyperplasia; Rats; Receptor, Cannabinoid, CB1

Benign prostatic hyperplasia (BPH) is a common disorder in men aged over 60 years and significantly contributes to the distressing lower urinary tract symptoms. Cucurbitacins are triterpene derivatives with diverse medicinal uses including prostate diseases. Cucurbitacin E glucoside was evaluated against testosterone-induced prostatic hyperplasia in mice. Our data indicate that it significantly inhibited the increase in prostate weight and prostate index. The compound ameliorated histopathological changes in prostatic architecture and inhibited the increase in glandular epithelial length induced by testosterone. These results were confirmed by decreased expression of cyclin D1 in prostatic tissues compared to those obtained from the testosterone-alone group. Also, it showed significant antioxidant activity as evidenced by inhibiting lipid peroxides accumulation, glutathione depletion and superoxide exhaustion. Further, it exhibited anti-inflammatory activity as it decreased cyclooxygenase-2 and interleukin-1β protein expression in prostatic tissues. Masson's trichrome staining of prostate sections indicated obvious antifibrotic activity that was supported by decreased α-smooth muscle actin expression. In conclusion, Cucurbitacin E glucoside inhibits testosterone-induced experimental BPH in mice due to, at least partly, its antiproliferative, antioxidant, anti-inflammatory, and antifibrotic effects.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Citrullus colocynthis; Cyclin D1; Disease Models, Animal; Glucosides; Male; Mice; Prostatic Hyperplasia; Testosterone; Triterpenes

Prostate cancer (PC) is common cancer worldwide. Several markers have been developed to differentiate between benign prostatic hyperplasia (BPH) from PC. A descriptive retrospective hospital-based study aimed at determining the expression of Cyclin D1 in BPH and PC. The study took place at different histopathology laboratories in Khartoum state, Sudan, from December 2016 to January 2019. Formalin-fixed paraffin-embedded blocks were sectioned and fixed in 3-aminopropyltriethoxysilane coated slides incubated into primary antibody for Cyclin D1. The assessment of immunoreactivity of Cyclin D1 of each section was done using the Gleason scoring system.. A total of 153 males' prostate sections included in this study, of them, 120 (78.4%) were PC, and 33 (21.6%) were BPH. Their age ranged from 45 to 88 years, mean age was 66.19 ± 8.599. 142 (92.8%) did not have a family history of PC, while 11 (7.2%) patients reported having a family history. The Gleason scoring showed a total of 81 (52.9%) patients with high-grade and 39 (25.5%) with low-grade. 118 (97.5%) patients had PC showed positive results for Cyclin D1, while BPH was 3 (2.5%). P value < 0.001. Cyclin D1 staining was associated with high-grade Gleason score and perineural invasion, P value 0.001.

Topics: Aged; Aged, 80 and over; Cyclin D1; Humans; Immunohistochemistry; Male; Middle Aged; Neoplasm Grading; Prostatic Hyperplasia; Prostatic Neoplasms; Retrospective Studies; Sudan

Benign prostatic hyperplasia (BPH) is a widespread disorder in elderly men. Cinnamaldehyde, which is a major constituent in the essential oil of cinnamon, has been previously reported to reduce xanthine oxidase activity, in addition to its anti-inflammatory, anti-oxidant, and anti-proliferative activities. Our study was designed to investigate the potential modulatory effects of cinnamaldehyde on testosterone model of BPH in rats through reduction of uric acid level, and suppression of IL-6/JAK1/STAT3 signaling pathway. Cinnamaldehyde (40 and 75 mg/kg) was orally administered to male Wistar rats for 3 weeks, and concurrently with testosterone (3 mg/kg, s.c.) from the second week. Cinnamaldehyde ameliorated the elevation in prostatic weight and index compared to rats treated with testosterone only, that was also confirmed by alleviation of histopathological changes in prostate architecture. The protective mechanisms of cinnamaldehyde were elucidated through inhibition of xanthine oxidase activity and reduced uric acid level. That was accompanied by reduction of the pro-inflammatory cytokines; interleukin-6 (IL-6), IL-1β, tumor necrosis factor-alpha (TNF-α), and the nuclear translocation of the transcription factor NF-κB p65, that could be attributed also to the enhanced anti-oxidant defense by cinnamaldehyde. The protein expression of JAK1, which is IL-6 receptor linked protein, was reduced with subsequently reduced activation of STAT3 protein. That eventually suppressed the formation of the proliferation protein cyclin D1, while elevated Bax/Bcl2 ratio. It can be concluded that reducing uric acid level through xanthine oxidase inhibition and suppression of the inflammatory signaling cascade; IL-6/JAK1/STAT3; by cinnamaldehyde could be a novel and promising therapeutic approach against BPH.

Topics: Acrolein; Animals; Biomarkers; Cell Proliferation; Cyclin D1; Gene Expression Regulation; Immunohistochemistry; Interleukin-6; Janus Kinase 1; Male; Prostate; Prostatic Hyperplasia; Rats; RNA, Messenger; STAT3 Transcription Factor; Uric Acid; Xanthine Oxidase

Benign prostatic hyperplasia (BPH) is a common chronic disease of the urinary system among elderly men. Especially, the metabolic imbalance of androgen in elderly men is one of the leading causes of BPH. Dihydrotestosterone (DHT) and converted testosterone by 5-α reductase type 2 (5AR2), binding with androgen receptor (AR), affect prostate proliferation and growth. In BPH, levels of androgen signaling-related protein expression are shown highly. Androgen signaling induces the overexpression of prostate-specific antigen (PSA) and cell proliferation factor such as proliferating cell nuclear antigen (PCNA) and cyclin D1. Grape skin anthocyanins are well known for their antioxidative, anti-cancer, anti-diabetes, anti-inflammatory, antimicrobial, and anti-aging activities. Polymerized anthocyanin (PA) downregulated the expression of androgen signaling-related proteins such as 5AR2, AR, and PSA in LNCaP cell lines. Furthermore, we investigated the effects on PA in testosterone propionate-induced BPH rat experiments. The oral administration of PA decreased the prostate weight in rats with TP-induced BPH. PA decreased the AR, 5AR2, SRC1, PSA, PCNA, and cyclin D1 expression in prostate tissues and the serum DHT levels, ameliorated the BPH-mediated increase of Bcl-2 expression, and increased the Bax expression. These results suggest that PA may be a potential natural therapeutic agent for BPH treatment.

Topics: Androgens; Animals; Anthocyanins; Cell Line, Tumor; Cyclin D1; Down-Regulation; Fruit; Gene Expression Regulation, Neoplastic; Humans; Male; Proliferating Cell Nuclear Antigen; Prostatic Hyperplasia; Rats; Rats, Sprague-Dawley; Signal Transduction; Up-Regulation; Vitis

Paljung-san is a traditional herbal medicine used widely for the treatment of urogenital diseases in East Asia. However, scientific evidence of the efficacy of Paljung-san and its mechanisms of action against benign prostatic hyperplasia (BPH) is not clearly established.. We investigated the inhibitory effect of Paljung-san water extract (PSWE) and its mechanisms against BPH in vitro and in vivo.. Active compounds of PSWE were analyzed quantitatively by High-performance liquid chromatography (HPLC). For in vitro study, PSWE treated BPH-1 cells were used to perform western blot analysis, cell cycle analysis and enzyme-linked immunosorbent assay. For in vivo BPH model, male rats were subcutaneously injected with 10 mg/kg of testosterone propionate (TP) every day for four weeks. 200 and 500 mg/kg of PSWE was administrated daily by oral gavage with s.c. injection of TP, respectively.. HPLC revealed that PSWE contains 1.21, 1.18, 2.27, 3.56, 4.23, 3.00, 6.78, and 0.004 mg/g of gallic acid, 5-caffeoylquinic acid, chlorogenic acid, geniposide, liquiritin apioside, liquiritin, glycyrrhizin, and chrysophanol components, respectively. In human BPH-1 cells, PSWE treatment reduced cell proliferation through arresting the cell cycle in the DNA synthesis phase. Moreover, PSWE suppressed prostaglandin E. PSWE attenuates the progression of BPH through anti-proliferative, anti-inflammatory and anti-oxidant activities in vitro and in vivo. Therefore, these data provide the scientific evidence of pharmacological efficacy of PSWE against BPH.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Cell Line; Cell Proliferation; Cell Survival; Cyclin D1; Cyclooxygenase 2; Dihydrotestosterone; Dinoprostone; Glutathione Reductase; Humans; Male; Malondialdehyde; Medicine, Traditional; Oxidative Stress; Phytotherapy; Plant Extracts; Proliferating Cell Nuclear Antigen; Prostatic Hyperplasia; Rats, Sprague-Dawley; Reactive Oxygen Species

Benign prostatic hyperplasia (BPH) is characterized by the proliferation of stromal and epithelial cell types in the prostate, and interactions between the two types of cells. We demonstrated previously that proliferation of prostate stromal cells was induced by BPH epithelial cells in response to Trichomonas vaginalis (Tv) infection via crosstalk with mast cells. In this study, we investigated whether IL-6 released by the proliferating stromal cells in turn induce the BPH epithelial cells to multiply. When culture supernatants of the proliferating prostate stromal cells were added to BPH epithelial cells, the latter multiplied, and expression of cyclin D1, FGF2 and Bcl-2 increased. Blocking the IL-6 signalling pathway with anti-IL-6R antibody or JAK1/2 inhibitor inhibited the proliferation of the BPH epithelial cells and reduced the expression of IL-6, IL-6R and STAT3. Also, epithelial-mesenchymal transition was detected in the proliferating BPH epithelial cells. In conclusion, IL-6 released from proliferating prostate stromal cells induced by BPH epithelial cells infected with Tv in turn induces multiplication of the BPH epithelial cells. This result provides first evidence that the inflammatory microenvironment of prostate stromal cells resulting from Tv infection induces the proliferation of prostate epithelial cells by stromal-epithelial interaction.

Topics: bcl-Associated Death Protein; Cell Proliferation; Cyclin D1; Epithelial Cells; Epithelial-Mesenchymal Transition; Fibroblast Growth Factor 2; Humans; Interleukin-6; Male; Mast Cells; Prostate; Prostatic Hyperplasia; Signal Transduction; STAT3 Transcription Factor; Stromal Cells; Trichomonas Infections; Trichomonas vaginalis

Previous studies by our group have shown that low intra-prostatic dihydrotestosterone (DHT) induced BPH epithelial cells (BECs) to recruit CD8+ T cells. However, the influence of the recruited CD8+ T cells on BECs under a low androgen level is still unknown. Here, we found CD8+ T cells have the capacity to promote proliferation of BECs in low androgen condition. Mechanism dissection revealed that interaction between CD8+ T cells and BECs through secretion of CCL5 might promote the phosphorylation of STAT5 and a higher expression of CCND1 in BECs. Suppressed CCL5/STAT5 signals via CCL5 neutralizing antibody or STAT5 inhibitor Pimozide led to reverse CD8+ T cell-enhanced BECs proliferation. IHC analysis from Finasteride treated patients showed PCNA expression in BECs was highly correlated to the level of CD8+ T cell infiltration and the expression of CCL5. Consequently, our data indicated infiltrating CD8+ T cells could promote the proliferation of BECs in low androgen condition via modulation of CCL5/STAT5/CCND1 signaling. The increased secretion of CCL5 from the CD8+ T cells/BECs interaction might help BECs survive in a low DHT environment. Targeting these signals may provide a new potential therapeutic approach to better treat BPH patients who failed the therapy of 5α-reductase inhibitors.

Topics: CD8-Positive T-Lymphocytes; Cell Line; Cell Proliferation; Chemokine CCL5; Coculture Techniques; Cyclin D1; Dihydrotestosterone; Epithelial Cells; Finasteride; Gene Expression Regulation; Humans; Male; Phosphorylation; Pimozide; Prostatic Hyperplasia; Signal Transduction; STAT5 Transcription Factor

Previous studies by our group showed that Qianliening capsules (QC), a clinically proven effective traditional Chinese formulation that has long been used in the treatment of benign prostatic hyperplasia (BPH), is capable of inhibiting BPH in vivo and in vitro via the promotion of apoptosis, suppression of the EGFR/STAT3 signaling pathway and regulating the expression of sex hormones as well as their receptors. However, the mechanism of its anti-BPH activity has remained to be fully elucidated. The present study aimed to investigate the mechanism underlying the anti-proliferative effect of QC in vivo and in vitro. Castrated male Sprage-Dawley (SD) rats where subcutaneously injected with testosterone propionate and the WPMY-1 cell line was stimulated with basic fibroblast growth factor in order to generate BPH in vivo and in vitro separately, both of which were then subjected to QC treatment. Finasteride was used as a positive control drug for the in vivo study. In the present study, it was found that treatment with QC or finasteride significantly reduced the prostatic index (PI=prostate wet weight/body weight x 100) in a rat model of BPH (P<0.05). In addition, reverse transcription quantitative polymerase chain reaction (RT-PCR) and western blot analyses showed that QC or finasteride treatment significantly inhibited model construction-induced upregulation of expression of proliferating cell nuclear antigen, cyclin D1 and cyclin-dependent kinase 4 in prostatic tissues of rats with BPH (P<0.05). The in vitro study further proved that QC exhibited anti-proliferative properties via G1/S cell cycle arrest in the WPMY-1 cell line, as evidenced by colony formation, flow cytometric cell cycle, immunoblot and RT-PCR analyses. In conclusion, the present study demonstrated that inhibition of cell proliferation via G1/S cell cycle arrest may be one of the underlying mechanisms of the effect of QC on BPH.

Topics: Animals; Capsules; Cell Line; Cell Proliferation; Cell Survival; Cyclin D1; Cyclin-Dependent Kinase 4; Disease Models, Animal; Drugs, Chinese Herbal; Fibroblast Growth Factor 2; G1 Phase Cell Cycle Checkpoints; Male; Proliferating Cell Nuclear Antigen; Prostate; Prostatic Hyperplasia; Rats; Rats, Sprague-Dawley; S Phase Cell Cycle Checkpoints; Signal Transduction

Persistent activation of Survivin and its overexpression contribute to the formation, progression and metastasis of several different tumor types. Therefore, Survivin is an ideal target for RNA interference mediated-growth inhibition. Blockade of Survivin using specific short hairpin RNAs (shRNA) can significantly reduce prostate tumor growth. RNA interference does not fully ablate target gene expression, owing to the idiosyncrasies associated with shRNAs and their targets. To enhance the therapeutic efficacy of Survivin-specific shRNA, we employed a combinatorial expression of Survivin-specific shRNA and gene associated with retinoid-interferon-induced mortality-19 (GRIM-19). Then, the GRIM-19 coding sequences and Survivin-specific shRNAs were used to create a dual expression plasmid vector and were carried by an attenuated strain of Salmonella enteric serovar typhimurium (S. typhimurium) to treat prostate cancer in vitro and in vivo. We found that the co-expressed Survivin-specific shRNA and GRIM-19 synergistically and more effectively inhibited prostate tumor proliferation and survival, when compared with treatment with either single agent alone in vitro and in vivo. This study has provided a novel cancer gene therapeutic approach for prostate cancer.

Topics: Animals; Apoptosis; Apoptosis Regulatory Proteins; bcl-X Protein; Carcinoma; Caspase 3; Cell Line, Tumor; Cyclin D1; Gene Expression; Genetic Therapy; Humans; Inhibitor of Apoptosis Proteins; Ki-67 Antigen; Male; Mice; NADH, NADPH Oxidoreductases; Plasmids; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms; Proto-Oncogene Proteins c-myc; RNA, Small Interfering; Salmonella typhimurium; STAT3 Transcription Factor; Survivin; Vascular Endothelial Growth Factor A

Areca nut chewing is the fourth most popular habit in the world due to its effects as a mild stimulant, causing a feeling of euphoria and slightly heightened alertness. Areca nuts contain several alkaloids and tannins, of which arecoline is the most abundant and known to have several adverse effects in humans, specially an increased risk of oral cancer. On evaluating the effects of arecoline on the male endocrine physiology in Wistar rats, it was found that arecoline treatment led to an overall enlargement and increase in the wet weight of the prostate gland, and a two-fold increase in serum gonadotropin and testosterone levels. Since the prostate is a major target for testosterone, the consequences of arecoline consumption were studied specifically in the prostate gland. Arecoline treatment led to an increase in the number of rough endoplasmic reticulum and reduction of secretory vesicles, signifying a hyperactive state of the prostate. Increased expression of androgen receptors in response to arecoline allowed for enhanced effect of testosterone in the prostate of treated animals, which augmented cell proliferation, subsequently confirmed by an increase in the expression of Ki-67 protein. Cellular proliferation was also the outcome of concomitant over expression of the G(1)-to-S cell cycle regulatory proteins, cyclin D1 and CDK4, both at the transcriptional and translational levels. Taken together, the findings provide the first evidence that regular use of arecoline may lead to prostatic hyperplasia and hypertrophy, and eventually to disorders associated with prostate enlargement.

Topics: Animals; Arecoline; Blotting, Western; Cell Growth Processes; Cyclin D1; Cyclin-Dependent Kinase 4; Dose-Response Relationship, Drug; Flow Cytometry; Follicle Stimulating Hormone; Immunohistochemistry; Ki-67 Antigen; Luteinizing Hormone; Male; Microscopy, Electron, Transmission; Prostate; Prostatic Hyperplasia; Rats; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction; RNA; Testosterone

Prostasin is down-regulated during inflammation and in invasive cancers, and plays a role in regulation of inflammatory gene expression and invasion.. We used the human benign prostatic hyperplasia cell line BPH-1 to investigate gene expression changes associated with siRNA-mediated loss of prostasin expression. Quantitative PCR and/or western blotting were used to evaluate the expression changes of iNOS, ICAM-1, cyclin D1, IL-6, and IL-8. Gene expression changes were also evaluated in the presence of a PAR-2 antagonist. The PC-3 human prostate cancer cell line was used for evaluation of gene expression in response to prostasin re-expression.. Prostasin silencing in BPH-1 was associated with up-regulation of iNOS, ICAM-1, IL-6, and IL-8, and down-regulation of cyclin D1; as well as reduced proliferation and invasion. The iNOS up-regulation and cyclin D1 down-regulation associated with prostasin silencing were inhibited by a PAR-2 antagonist. Re-expression of prostasin, a serine active-site mutant, and a GPI-anchor-free mutant, in the PC-3 cells resulted in PAR-2 and cyclin D1 transcription up-regulation. Transcription up-regulation of IL-6 and IL-8 was associated with re-expression of the serine active-site mutant prostasin in the PC-3 cells. Transcription up-regulation of IL-8, but to a lesser extent, was also observed in PC-3 cells expressing the wild-type prostasin. Expression of a serine protease active prostasin, GPI-anchored or anchor-free, prevented the IL-6 induction in response to PAR-2. The GPI-anchor-free prostasin also prevented the IL-8 induction.. Prostasin plays a negative regulatory role on PAR-2-mediated signaling in prostate epithelial cells.

Topics: Blotting, Western; Cell Line; Cell Proliferation; Cyclin D1; Down-Regulation; Epithelial Cells; Humans; Intercellular Adhesion Molecule-1; Interleukin-6; Interleukin-8; Male; Nitric Oxide Synthase Type II; Polymerase Chain Reaction; Prostate; Prostatic Hyperplasia; Receptor, PAR-2; RNA, Small Interfering; Serine Endopeptidases; Signal Transduction; Up-Regulation

Age-dependent epithelial cell hyperplasia in the dorsal and lateral lobes of Brown Norway rats is analogous to benign prostatic hyperplasia in aging men. A major question is whether differential lobe-specific and age-dependent proliferation of cells, rather than cell survival, contributes to the hyperplasia. Although serum testosterone (T) levels decline in aged rats, active cell proliferation was detected as Ki67-positive cells in the dorsal and lateral lobes. We determined whether androgens differentially affect cell proliferation and cell-cycle regulatory proteins in the prostate lobes of young and aged rats. Castrated rats were treated with different doses of T to restore serum levels to those of intact young or aged rats. Rates of cell proliferation, measured by 5-bromodeoxyuridine labeling, peaked after 3-d T treatment in all lobes. 5-bromodeoxyuridine-labeling indices were higher in the dorsal and lateral lobes of aged than of young rats with equivalent serum T levels. No age-dependent difference was seen in the ventral lobe. Cell proliferation was marked by increased levels of cyclins D1 and E and cyclin-dependent kinases 4 and 6, decreased p27 and increased phosphorylation of Rb. Levels of cyclins D1 and E were higher in the dorsal and lateral lobes of intact and T-treated aged than young rats. Confocal immunofluorescent microscopy documented changes in cyclin-dependent kinase 4 and cyclin D1 subcellular localization. Cyclin D1 nuclear localization correlated with the time frame for cell proliferation. In conclusion, rates of cell proliferation and levels of cell-cycle regulatory proteins that control the G1/S transition exhibit lobe-specific and age-dependent differences in response to androgens.

Topics: Age Factors; Animals; Castration; Cell Cycle Proteins; Cell Proliferation; Cyclin D1; Cyclin-Dependent Kinase 4; Disease Models, Animal; Epithelial Cells; G1 Phase; Gene Expression Regulation; Male; Organ Size; Organ Specificity; Prostate; Prostatic Hyperplasia; Rats; Rats, Inbred BN; S Phase; Testosterone; Tissue Distribution

CCND1 mRNA is alternatively spliced to produce 2 transcripts, and the splicing pattern may be modulated by a frequent A870G single-nucleotide polymorphism within the conserved splice donor site of exon 4. Several studies have suggested a significant association between the CCND1 genotype and onset or progression of various cancers. To investigate the correlation of the polymorphism with genetic susceptibility to PCa and its disease status, we examined the polymorphism in 214 cases of PCa, 234 cases of BPH and 254 male controls. The CCND1 A allele was more frequently observed in the PCa group (p = 0.015) and the BPH group (p = 0.018) than the control group. Men with the AA genotype had an increased risk of PCa (aOR = 1.93, 95% CI 1.13-3.30, p = 0.016) and BPH (aOR = 1.84, 95% CI 1.09-3.09, p = 0.023) compared to those with the GG genotype. No significant association was observed when men with the AG genotype were compared to those with the GG genotype (PCa: aOR = 1.00, 95% CI 0.65-1.54, BPH: aOR = 0.91, 95% CI 0.60-1.39). The risk of PCa associated with the AA genotype appeared to be stronger in men aged 73 years or younger (aOR = 2.89, 95% CI 1.38-6.01, p = 0.005), whereas no association was found in men older than 73 years (aOR = 1.02, 95% CI 0.44-2.34). No significant difference in genotype frequency was found among patients with low-, intermediate- and high-grade tumors (p = 0.730) or between patients with localized and metastatic PCa (p = 0.679). However, in patients with high-grade or metastatic PCa, a significantly increased risk associated with the AA genotype compared to controls was observed, while no significant results were found in those with low/intermediate or localized PCa. The A allele of the CCND1 A870G polymorphism was recessively associated with susceptibility to PCa and BPH in a Japanese population, giving a 2-fold increased risk of PCa and BPH in men with the AA genotype compared to those with the GG genotype. Although the risk of PCa associated with the AA genotype appeared to contribute especially to men aged 73 years or younger and the A allele may be associated with disease status of PCa, these conjectures require validation in future studies on a larger number of subjects.

Topics: Adenocarcinoma; Aged; Alternative Splicing; Case-Control Studies; Cyclin D1; Dinucleotide Repeats; Genetic Predisposition to Disease; Genotype; Humans; Male; Polymorphism, Genetic; Prostatic Hyperplasia; Prostatic Neoplasms; Risk Factors

The fundamental process in the development of benign prostatic hyperplasia (BPH) is a loss of homeostasis between cell proliferation and apoptosis. Prostatic smooth muscle cells contract under adrenergic control. The response of a cell to stretch may have a role in the pathogenesis of BPH.. Monolayer cultures of human prostatic stromal and epithelial cell lines were exposed to cyclic stretch for 48 hours.. Cyclic stretch conferred resistance to etoposide induced apoptosis. Underlying this apoptotic resistance was increased expression of the anti-apoptotic Bcl-2 family of proteins. As measured by thymidine incorporation, the rate of proliferation also increased in benign epithelial cells under cyclic stretch conditions. Furthermore, an increase in the production of platelet-derived growth factor by stromal cells and transforming growth factor-beta by epithelial cells occurred under such conditions.. The observed changes in proliferation and apoptosis may contribute to the understanding of BPH, ultimately leading to therapeutic and preventive applications.

Topics: Apoptosis; bcl-X Protein; Cell Division; Cells, Cultured; Cyclin D1; Epithelial Cells; Homeostasis; Humans; Male; Myeloid Cell Leukemia Sequence 1 Protein; Neoplasm Proteins; Physical Stimulation; Platelet-Derived Growth Factor; Prostate; Prostatic Hyperplasia; Proto-Oncogene Proteins c-bcl-2; Stromal Cells; Transforming Growth Factor beta

Overexpression of cyclin D1 has been documented in a number of human cancers. Increased expression of cyclin D1 can contribute to cellular transformation and abnormal proliferation.. Quantitative RT-PCR and/or Western blot analysis were used to determine the level of cyclin D1 expression in 96 human prostate tumors, 15 benign prostate hyperplasias, 4 prostate cancer cell lines, and 3 xenografts.. Our results demonstrate that 4.2% of the prostate tumors examined overexpressed cyclin D1 transcripts. In the cell lines, expression was normal, with the exception that reduced levels of cyclin D1 transcript and protein were observed in the DU145 cell line, as expected from cells with mutant RB. Normal levels of cyclin D1 were found in all xenograft tumors and BPH specimens examined.. These data show that overexpression of cyclin D1 occurs rarely in human prostate tumors. However, when overexpression of cyclin D1 does occur, it may identify a subset of tumors with a different molecular biology.

Topics: Blotting, Southern; Blotting, Western; Cyclin D1; DNA Primers; DNA, Neoplasm; Gene Expression Regulation, Neoplastic; Humans; Male; Prostatic Hyperplasia; Prostatic Neoplasms; Reverse Transcriptase Polymerase Chain Reaction; RNA, Neoplasm; Tumor Cells, Cultured