In:
Molecular Endocrinology, The Endocrine Society, Vol. 20, No. 10 ( 2006-10-01), p. 2382-2391
Abstract:
Mullerian inhibiting substance (MIS), a member of the TGFβ superfamily, causes regression of the Mullerian duct in male embryos. The presence of MIS type II and type I receptors in tissues and cell lines derived from the prostate suggests that prostate is a likely target for MIS. In this report, we demonstrate that MIS inhibits androgen-stimulated growth of LNCaP cells and decreases their survival in androgen-deprived medium by preventing cell cycle progression and inducing apoptosis. Expression of dominant-negative Smad1 reversed the ability of MIS to decrease LNCaP cell survival in androgen-deprived medium but not androgen-stimulated growth, whereas abrogation of nuclear factor-κB (NFκB) activation ablated the suppressive effects of MIS on both androgen-stimulated growth and androgen-independent survival. The effect of MIS on androgen-induced growth was not due to changes in androgen receptor expression. However, MIS suppressed androgen-stimulated transcription of prostate-specific antigen; ablation of NFκB activation reversed MIS-mediated suppression of prostate-specific antigen. These observations suggest that MIS regulates androgen-induced gene expression and growth in prostate cancer cells through a NFκB-dependent but Smad1-independent mechanism. Thus, MIS, in addition to potentially regulating prostate growth indirectly by suppressing testicular testosterone synthesis, may also be a direct regulator of androgen-induced gene expression and growth in the prostate at the cellular level.
Type of Medium:
Online Resource
ISSN:
0888-8809
,
1944-9917
DOI:
10.1210/me.2005-0480
Language:
English
Publisher:
The Endocrine Society
Publication Date:
2006
detail.hit.zdb_id:
1492112-1
