Prostate cancer is the most frequently diagnosed cancer and the second leading cause of cancer-related deaths in men in the United States 
. Currently there is no effective treatment for androgen-independent advanced prostate cancer 
. Mechanisms that enable prostate cancer cells to evade apoptosis may contribute to therapeutic resistance. Thus, increased levels of several growth factors, including FGF, EGF, IL-6 and GPCR agonists that activate anti-apoptotic signaling pathways, have been reported in androgen-independent prostate cancer 
. Anti-apoptotic signals could either post-translationally modify apoptosis regulatory proteins or change their expression levels. Indeed, increased expression of anti-apoptotic Bcl-2 proteins as well as inhibitors of apoptosis proteins (IAPs) in advanced prostate cancer has been reported 
. Also, we have recently shown that in prostate cancer cells, the pro-apoptotic Bcl-2 protein BAD plays a unique role as a convergence point of several anti-apoptotic signaling pathways that include constitutively active PI3K, activated EGFR and GPCR 
ntagonist causing cell d
eath, was initially identified in a yeast two hybrid screen interacting with Bcl-2 or Bcl-xl 
. BAD is a unique BH3-only family member in that its regulation is primarily mediated through its conserved phosphorylation sites (serines 112, 136, and 155 based on the mouse sequence)
. Phosphorylated BAD fails to bind Bcl-XL or Bcl-2 proteins, and has been considered an apoptosis sentinel inactivated by anti-apoptotic signals. Upon withdrawal of survival factors BAD becomes dephosphorylated, shifts the balance of pro- and anti-apoptotic Bcl proteins that triggers release of cytochrome c, SMAC and AIF from mitochondria and subsequently leads to apoptosis 
. Thereby, it would not be surprising if cancer cells decrease BAD expression.
A recent study has shown that BAD expression is elevated in prostatic carcinomas compared to low expression in normal prostatic epithelium 
. It seems counterintuitive that prostate cells would dedicate extra resources to maintain BAD phosphorylation instead of eliminating its expression. It is possible that in addition to regulating apoptosis, BAD might play a positive role in prostatic tumor growth.
Here we report that increased BAD expression stimulates proliferation of prostate cancer cells in tissue culture and prostate tumor growth in vivo. At the same time, BAD dephosphorylation increases sensitivity of prostate cancer cells to apoptosis. This combination of proliferative and apoptotic properties creates conditions for prostate cancer cells “addiction” to increased levels of phosphorylated BAD. Thus, kinases that phosphorylate BAD are plausible therapeutic targets.