Interaction of epidermal growth factor and transforming growth factor beta in human prostatic epithelial cells in culture

Sutkowski, Debra M.; Fong, Chau‐Jye; Sensibar, Julia A.; Rademaker, Alfred; Sherwood, Edward R.; Kozlowski, James M.; Lee, Chung

doi:10.1002/pros.2990210206

Cited by 74 publications

(41 citation statements)

References 8 publications

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“…TGF-b1 is a pluralistic factor that can inhibit proliferation, induce apoptosis, promote angiogenesis and suppress immunity, all of which can enhance tumour development, progression and invasiveness. [41][42][43][44][45][46] Therefore, our findings indicate TGF-b1 as another possible factor involved in zonal differences. IGF-1 stimulates cell proliferation and inhibits apoptosis [47][48][49][50] and has also been reported as a potent angiogenic factor.…”

Section: Differential Effects Of Pzsc and Tzsc On Pc3 Cellsmentioning

confidence: 54%

The differential effects of prostate stromal cells derived from different zones on prostate cancer epithelial cells under the action of sex hormones

Jiang

Han²,

Zhao³

et al. 2011

Asian J Androl

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It is well known that prostate cancer (PCa) occurs predominantly in the peripheral zone (PZ), whereas benign prostatic hyperplasia (BPH) typically develops in the transition zone. To identify possible mechanisms underlying zonal differences, we compared the effects of prostate stromal cells derived from the peripheral zone (PZsc) and the transition zone (TZsc) on a PCa epithelial cell line (PC3) in the presence of sex hormones. First, we observed that androgen receptor (AR) mRNA was more highly expressed in PZsc than TZsc when the cells were treated with dihydrotestosterone (DHT) and b-oestradiol (E2) (P,0.05). By ELISA, we looked for differences in the secretion of peptide growth factors from PZsc and TZsc. We found that keratinocyte growth factor (KGF) secretion increased with increasing concentrations of DHT (P,0.01) and was higher in PZsc than TZsc. Under treatment with DHT plus E2, PZsc secreted more transforming growth factor-b1 (TGF-b1) than TZsc, but this pattern was reversed when the cells were treated with E2 only. With increasing concentrations of DHT, insulin-like growth factor-1 (IGF-1) secretion increased in PZsc but decreased in TZsc. To further characterize the effects of PZsc and TZsc on PC3 cells, we developed a coculture model and performed MTT assays, Western blot analysis and real-time RT-PCR. We found that PZsc promoted PC3 cell proliferation and progression better than TZsc, particularly when treated with 10 nmol l 21 DHT plus 10 nmol l 21 E2. In conclusion, our data suggest that PZsc may have a greater capacity to induce PCa development and progression than TZsc via growth factors regulated by sex hormones. These findings provide possible mechanisms underlying zonal differences in prostate diseases, which may aid the search for novel therapeutic targets for PCa.

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Section: Differential Effects Of Pzsc and Tzsc On Pc3 Cellsmentioning

confidence: 54%

The differential effects of prostate stromal cells derived from different zones on prostate cancer epithelial cells under the action of sex hormones

Jiang

Han²,

Zhao³

et al. 2011

Asian J Androl

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“…Nevertheless, in primary cultures of normal prostatic epithelial cells, TGFb typically induces growth arrest and other phenotypic changes, but not apoptosis (Peehl et al 1994b). However, Sutkowski et al (1992) reported that TGFb induced apoptosis in primary cultures if the potent mitogen and survival factor, EGF, was deleted from the culture medium. This finding suggests that the activity of TGFb and/or the ability to undergo apoptosis in general depends on the local milieu of growth and survival factors.…”

Section: Apoptosismentioning

confidence: 99%

Primary cell cultures as models of prostate cancer development

Peehl¹

2005

Endocr Relat Cancer

152

142

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This review focuses on primary cultures of human prostatic epithelial cells and their applications as models of normal and malignant biological behavior. Current abilities to culture cells from normal tissues, from premalignant dysplastic lesions (prostatic intraepithelial neoplasia), from primary adenocarcinomas, and from metastases are described. Evidence for representation of the interrelated cells of the normal prostatic epithelium -stem cells, basal epithelial cells, secretory epithelial cells, transit amplifying cells and neuroendocrine cells -in primary cultures is presented. Comparisons between normal and cancer-derived primary cultures are made regarding biological activities relevant to carcinogenesis, such as proliferation, apoptosis, differentiation, senescence, adhesion, migration, invasion, steroid hormone metabolism, other metabolic pathways and angiogenesis. Analyses of tumor suppressor activity, differential gene expression and cytogenetics in primary cultures have revealed changes relevant to prostate cancer progression. Preclinical studies with primary cultures have provided information useful for designing new strategies for chemoprevention, chemotherapy, cytotoxin therapy, radiation therapy, gene therapy and imaging. While the behavior of normal primary cultures is often used as a basis for comparison with established, immortal prostate cancer cell lines, the most informative studies are performed with donor-matched pairs of normal and malignant primary cultures, grown under identical conditions. Challenges that remain to be addressed if the full potential of primary cultures as a model system is to be realized include isolation, culture and characterization of stem cells, improved methodology to induce or maintain a fully differentiated, androgen-responsive phenotype, and identification of cell surface antigens or other markers with which to purify pure populations of live cancer or premalignant cells apart from non-malignant epithelial cells prior to culture.

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“…Receptors for TGF 1 have also been identified in the human prostate cancer cell lines DU145 and PC-3 (Wilding et al 1989). TGF 1 has a mainly inhibitory effect on human prostatic fibroblasts and epithelial cells in culture (Sutkowski et al 1992, Story et al 1993. Our studies have confirmed this mainly inhibitory effect, which was most marked in cultures which contained low levels of FGF2.…”

Section: Figurementioning

confidence: 99%

“…TGF 1 and TGF 2 have been identified in human prostate and implicated in prostatic disease (Knabbe et al 1993, Truong et al 1993. Addition of TGF 1 to cultured prostatic epithelial and stromal cells has been reported to inhibit proliferation in both cell types (Sutkowski et al 1992). However, low levels of TGF 1 have been shown to result in small increases (1·5-fold) in cell proliferation in both stroma and epithelium (Collins et al 1996).…”

Section: Introductionmentioning

confidence: 99%

Transforming growth factor-beta1 up-regulates p15, p21 and p27 and blocks cell cycling in G1 in human prostate epithelium

Robson¹,

Gnanapragasam²,

Byrne³

et al. 1999

Journal of Endocrinology

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Transforming growth factor-1 (TGF 1) is inhibitory to most epithelia, but its role in the control of proliferation of prostatic epithelium is unclear. In some cells, TGF 1 inhibition is achieved by up-regulation of cyclindependent kinase (cdk) inhibitors including p15, p21 and p27.Our aims were to determine whether the effects of TGF 1 on human prostatic epithelial cell cycle kinetics were mediated by alterations in the levels of the cdk inhibitors p15, p16, p21 and p27 and hypophosphorylated retinoblastoma protein (Rb).Human prostatic epithelial cells in primary culture were grown in the presence of TGF 1 (0-10 ng/ml) for up to 4 days and proliferation assessed using a [ 3 H]thymidine uptake assay. Levels of p15, p16, p21 and p27 were measured at both mRNA and protein level by means of a reverse transcriptase PCR-based assay and Western analysis. Rb and cdk2 levels were measured.Exogenous TGF 1 (0-5 ng/ml) inhibited proliferation. This was associated with blocking of the cell cycle at G1, and up to 4-fold increases in p15, p21 and p27 mRNA levels, but no change was observed in p16 mRNA levels; these changes were not blocked by cycloheximide. Increased levels of p15, p21 and p27 protein were also accompanied by increased levels of hypo-phosphorylated Rb and decreased cdk2 kinase activity.TGF 1 has mainly inhibitory effects on benign human prostatic epithelium, which are caused by up-regulation of cdk inhibitors, hypo-phosphorylation of Rb and delaying of the cell cycle in G1.

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Interaction of epidermal growth factor and transforming growth factor beta in human prostatic epithelial cells in culture

Cited by 74 publications

References 8 publications

The differential effects of prostate stromal cells derived from different zones on prostate cancer epithelial cells under the action of sex hormones

The differential effects of prostate stromal cells derived from different zones on prostate cancer epithelial cells under the action of sex hormones

Primary cell cultures as models of prostate cancer development

Transforming growth factor-beta1 up-regulates p15, p21 and p27 and blocks cell cycling in G1 in human prostate epithelium

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