Regulation of rat prostate stromal cell myodifferentiation by androgen and TGF‐β1

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Abstract
BACKGROUND Myodifferentiation of stromal cells is a key step in prostate development and is a hallmark of reactive stroma in prostate cancer. Little is known about regulatory mechanisms, however, prostate stromal cells are androgen-regulated and TGF-β1 is a known stimulator of stromal myodifferentiation. The PS-1 rat prostate stromal cell line expresses androgen receptor, and exhibits androgen-regulated gene expression and proliferation. TGF-β1 inhibits androgen action in PS-1 cells through translocation of androgen receptor from the nucleus to the cytoplasm. The present study was conducted to determine whether myodifferentiation of PS-1 cells is regulated by androgen and TGF-β1, and how myodifferentiation affects androgen receptor localization and cell proliferation. METHODS PS-1 cell cultures were exposed to physiological concentrations of dihydrotestosterone, TGF-β1, and combinations of both in chemically defined medium. Immunocytochemistry and Western blotting for smooth muscle α-actin filament formation, smooth muscle α-actin protein levels, calponin expression, PCNA index, and androgen receptor localization were performed. RESULTS Dihydrotestosterone (DHT) and TGF-β1 each separately promoted PS-1 myodifferentiation. A combination did not affect the rate of differentiation, however, the level of α-actin protein was elevated and PCNA was decreased in co-stimulated conditions. TGF-β1 induction resulted in a transient translocation of androgen receptor from the nucleus to the cytoplasm during differentiation followed by a resumed nuclear localization in myodifferentiated cells. CONCLUSIONS These data indicate that a complex cross-talk mechanism exists between androgen and TGF-β1 signaling in prostate stromal cells that affects cell proliferation and myodifferentiation. These findings also suggest that androgen and TGF-β1 interactions may cooperatively regulate myodifferentiation of stromal cells in the stromal response in prostate cancer.
Funding Information
  • NIH (RO1-CA58093, RO1-DK45909, U01-CA84296, SPORE-CA58204)

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