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This version published online on December 18, 2003
Molecular Endocrinology, doi:10.1210/me.2003-0360
Molecular Endocrinology Vol. 0, No. 2003 200303601-
doi:10.1210/me.2003-0360
Copyright © 2003 by the Endocrine Society.
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Submitted on September 16, 2003
Accepted on December 11, 2003

Mutually antagonistic effects of androgen and activin in the regulation of prostate cancer cell growth

Jennifer L. Carey1, Laura M. Sasur1, Hirofumi Kawakubo1, Vandana Gupta1, Benjamin Christian1, Paul M. Bailey1, and Shyamala Maheswaran1*

1 Pediatric Surgical Research Laboratories, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114

* To whom correspondence should be addressed. E-mail: maheswaran{at}helix.mgh.harvard.edu.

Activin, a member of the TGF{beta} superfamily, is expressed in the prostate and inhibits growth. We demonstrate that the effects of activin and androgen on regulation of prostate cancer cell growth are mutually antagonistic. In the absence of androgen, activin induced apoptosis in the androgen-dependent human prostate cancer cell line LNCaP, an effect suppressed by androgen administration. Although activin by itself did not alter the cell cycle distribution, it potently suppressed androgen-induced progression of cells into S-phase of the cell cycle and thus inhibited androgen-stimulated growth of LNCaP cells. Expression changes in cell cycle regulatory proteins such as Rb, E2F-1 and p27 demonstrated a strong correlation with the mutually antagonistic growth regulatory effects of activin and androgen. The inhibitory effect of activin on growth was independent of SSVS motif phosphorylation of Smad3. Despite their antagonistic effect on growth, activin and androgen co-stimulated the expression of PSA through a Smad3-mediated mechanism. These observations indicate the existence of a complex crosstalk between activin and androgen signaling in regulation of gene expression and growth of the prostate.
Key words: Activin A • rogen • prostate cancer • PSA • Smad3

NURSA Molecule Pages Link:

Ligands:   Dihydrotestosterone  |  R1881



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