Abstract
This study investigated the hypothesis that, in benign prostatic hyperplasia (BPH), upregulated oestrogen receptors (ER) and the action of androgens differentially regulate expression of stromal growth factors. Eight human prostatic stromal cell strains were subjected to a procedure to upregulate their ER by exposing them to 1 μmol 17β-estradiol for 10 days followed by passage and growth in the absence of steroids. Four of the cell strains instead received 100 nmol dihydrotestosterone for 48 h. Immunoexpression of ERα, AR and six growth factors was quantified by flow cytometry in each case. Expression of ERα was significantly increased in six of eight cell strains. Expressions of six growth factors (FGF-2, FGF-7, IGF-1, TGF-β1 NGF and e NOS) were elevated but only for FGF-7 was it significant. There was a significant positive correlation between the change in ERα and the change in FGF-2 and FGF-7, but not the other growth factors. Exposure to dihydrotestosterone reduced expression of ERα and all six growth factors, compared with oestrogen-treated cells but not significantly. It is concluded that upregulated ERα in prostatic stroma may have a greater modulating influence on synthesis of certain growth factors than the direct action of androgens and, by enhancing synthesis of FGF-2 and FGF-7, could play a significant role in the development of BPH.
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Acknowledgements
The Prostate Research Group acknowledges support of the Medical Research Council and the National Cancer Research Institute. This work was supported by a grant from the North West Cancer Research Fund to Y Ke and CS Foster. NP Rhodes is supported, in part, by the Engineering and Physical Science Research Council. We thank Mrs Jill Gosney for typing the manuscript and Mr AJ Williams for preparing the figures.
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Smith, P., Rhodes, N., Ke, Y. et al. Relationship between upregulated oestrogen receptors and expression of growth factors in cultured, human, prostatic stromal cells exposed to estradiol or dihydrotestosterone. Prostate Cancer Prostatic Dis 7, 57–62 (2004). https://doi.org/10.1038/sj.pcan.4500692
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DOI: https://doi.org/10.1038/sj.pcan.4500692
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