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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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
Michael J
MJ
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
Larsen
Melinda
M
Dang
Truong D
TD
Ressler
Steven J
SJ
Tuxhorn
Jennifer A
JA
Rowley
David R
DR
D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D001692:Biological Transport; D002454:Cell Differentiation / Q000187:drug effects; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D013196:Dihydrotestosterone / Q000494:pharmacology*; D008297:Male; D009130:Muscle, Smooth / Q000166:cytology*; D011467:Prostate / Q000166:cytology* / Q000378:metabolism; D051381:Rats; D011944:Receptors, Androgen / Q000378:metabolism; D017154:Stromal Cells / Q000166:cytology*; D013552:Swine; D013997:Time Factors; D014018:Tissue Distribution; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1
D000728:Androgens; D011944:Receptors, Androgen; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D013196:Dihydrotestosterone