Prostate Cancer Research Today is a free monthly online journal that collates and summarizes the latest research about Prostate Cancer, including details on symptoms, genetics, screening, treatment, information.

c-Fos as a proapoptotic agent in TRAIL-induced apoptosis in prostate cancer cells.

Zhang X, Zhang L, Yang H, Huang X, Otu H, Libermann TA, DeWolf WC, Khosravi-Far R, Olumi AF

Department of Urology, Massachusetts General Hospital, Boston, MA 02114, USA.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)/Apo-2L promotes apoptosis in cancer cells while sparing normal cells. Although many cancers are sensitive to TRAIL-induced apoptosis, some evade the proapoptotic effects of TRAIL. Therefore, differentiating molecular mechanisms that distinguish between TRAIL-sensitive and TRAIL-resistant tumors are essential for effective cancer therapies. Here, we show that c-Fos functions as a proapoptotic agent by repressing the antiapoptotic molecule c-FLIP(L). c-Fos binds the c-FLIP(L) promoter, represses its transcriptional activity, and reduces c-FLIP(L) mRNA and protein levels. Therefore, c-Fos is a key regulator of c-FLIP(L), and activation of c-Fos determines whether a cancer cell will undergo cell death after TRAIL treatment. Strategies to activate c-Fos or inhibit c-FLIP(L) may potentiate TRAIL-based proapoptotic therapies.

Published 2 October 2007 in Cancer Res, 67(19): 9425-34.
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