Regulation of rat prostate stromal cell myodifferentiation by androgen and TGF-beta1.

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-beta1 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-beta1 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-beta1, and how myodifferentiation affects androgen receptor localization and cell proliferation. PS-1 cell cultures were exposed to physiological concentrations of dihydrotestosterone, TGF-beta1, and combinations of both in chemically defined medium. Immunocytochemistry and Western blotting for smooth muscle alpha-actin filament formation, smooth muscle alpha-actin protein levels, calponin expression, PCNA index, and androgen receptor localization were performed. Dihydrotestosterone (DHT) and TGF-beta1 each separately promoted PS-1 myodifferentiation. A combination did not affect the rate of differentiation, however, the level of alpha-actin protein was elevated and PCNA was decreased in co-stimulated conditions. TGF-beta1 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. These data indicate that a complex cross-talk mechanism exists between androgen and TGF-beta1 signaling in prostate stromal cells that affects cell proliferation and myodifferentiation. These findings also suggest that androgen and TGF-beta1 interactions may cooperatively regulate myodifferentiation of stromal cells in the stromal response in prostate cancer.

Gerdes MJ ，Larsen M ，Dang TD ，Ressler SJ ，Tuxhorn JA ，Rowley DR ... -  《PROSTATE》

Transforming growth factor-beta1 induces nuclear to cytoplasmic distribution of androgen receptor and inhibits androgen response in prostate smooth muscle cells.

Gerdes MJ ，Dang TD ，Larsen M ，Rowley DR ... -  《ENDOCRINOLOGY》

Androgen and prostatic stroma.

Niu YJ ，Ma TX ，Zhang J ，Xu Y ，Han RF ，Sun G ... -  《ASIAN JOURNAL OF ANDROLOGY》

Estrogen induction of smooth muscle differentiation of human prostatic stromal cells is mediated by transforming growth factor-beta.

Hong JH ，Song C ，Shin Y ，Kim H ，Cho SP ，Kim WJ ，Ahn H ... -  《JOURNAL OF UROLOGY》

TGF-beta signaling and androgen receptor status determine apoptotic cross-talk in human prostate cancer cells.

Zhu ML ，Partin JV ，Bruckheimer EM ，Strup SE ，Kyprianou N ... -  《PROSTATE》