ORIGINAL ARTICLE

Cell Research (2007): 531-536
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Up-regulation of Bcl-2 is required for the progression of prostate cancer cells from an androgen-dependent to an androgen-independent growth stage

Yuting Lin¹, Junichi Fukuchi^2,3, Richard A Hiipakka², John M Kokontis² and Jialing Xiang¹

Correspondence: Jialing Xiang Tel: +312-567-3491; Fax: +312-567-3494 E-mail: xiang@iit.edu

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Bcl-2 is an anti-apoptotic oncoprotein and its protein levels are inversely correlated with prognosis in many cancers. However, the role of Bcl-2 in the progression of prostate cancer is not clear. Here we report that Bcl-2 is required for the progression of LNCaP prostate cancer cells from an androgen-dependent to an androgen-independent growth stage. The mRNA and protein levels of Bcl-2 are significantly increased in androgen-independent prostate cancer cells. shRNA-mediated gene silencing of Bcl-2 in androgen-independent prostate cancer cells promotes UV-induced apoptosis and suppresses the growth of prostate tumors in vivo. Growing androgen-dependent cells under androgen-deprivation conditions results in formation of androgen-independent colonies; and the transition from androgen-dependent to androgen-independent growth is blocked by ectopic expression of the Bcl-2 antagonist Bax or Bcl-2 shRNA. Thus, our results demonstrate that Bcl-2 is not only critical for the survival of androgen-independent prostate cancer cells, but is also required for the progression of prostate cancer cells from an androgen-dependent to an androgen-independent growth stage.

Cell Research (2007) 17:531–536 doi: 10.1038/cr.2007.12; published online 3 April 2007

Keywords: Bcl-2, prostate cancer progression, apoptosis, androgen-dependtance