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Prostate. 2008 Dec 1;68(16):1725-33. doi: 10.1002/pros.20839.

NF-kappaB2/p52 enhances androgen-independent growth of human LNCaP cells via protection from apoptotic cell death and cell cycle arrest induced by androgen-deprivation.

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  • 1Department of Urology and Cancer Center, University of California School of Medicine at Davis, California 96817, USA.

Abstract

PURPOSE:

Androgen-deprivation therapy only causes a temporary regression of prostate cancer, as all tumors will eventually progress to refractory to hormonal therapy after 1-3 years of treatment. The underlying mechanisms of prostate cancer androgen refractory progression are incompletely understood. In this study, we employed in vitro as well as in vivo models to examine the role of NF-kappaB2/p52 in prostate cancer growth and androgen independent progression.

EXPERIMENTAL DESIGN:

The effects of NF-kappaB2/p52 on cell growth, androgen responsiveness, cell cycle and apoptosis were examined in androgen sensitive LNCaP cells. The effect of NF-kappaB2/p52 on tumor growth was examined in intact and castrated male mice.

RESULTS:

Overexpression of NF-kappaB2/p52 enhances androgen-sensitive LNCaP human prostate cancer cell growth and clonogenic ability in androgen-deprived condition in vitro. NF-kappaB2/p52 induced androgen-independent growth is through protecting LNCaP cells from apoptotic cell death and cell cycle arrest induced by androgen-deprivation. In addition, NF-kappaB2/p52 stimulates Cyclin D1 expression and knock down of Cyclin D1 expression by siRNA abolished NF-kappaB2/p52-induced cell growth in vitro. Adenoviral mediated NF-kappaB2/p52 expression in LNCaP cells enhances tumor growth in intact male nude mice and induces tumor growth in castrated male nude mice, suggesting that overexpression of NF-kappaB2/p52 induces androgen-independent growth of androgen-sensitive LNCaP cells.

CONCLUSIONS:

Overexpression of NF-kappaB2/p52 protects androgen sensitive LNCaP cells from apoptotic cell death and cell cycle arrest induced by androgen-deprivation. NF-kappaB2/p52 activation induces androgen-independent growth in vitro and in vivo.

PMID:
18781579
[PubMed - indexed for MEDLINE]
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