Prostate cancer: JunD, Gadd45a and Gadd45g as therapeutic targets.

摘要

Prostate cancer is among the most prevalent malignancies in older men and a frequent cause of death. In addition to prostate-specific antigen (Psa) and Gleason grading, several molecular biomarkers have been proposed to predict outcome in patients with prostate cancer. However, few of these biomarkers are used to guide clinical prognostic/ diagnostic decision-making, since prostate cancer molecular pathology remains largely unknown. Nevertheless, plasma IL-6 and soluble IL-6 receptor (IL-6sR) levels are known to be significantly elevated in patients with met-astatic, hormone refractory prostate cancer, and their levels in blood are predictive of prostate cancer progression and poor outcome.Zerbini and colleagues have previously shown that increased expression of the IL-6 gene in prostate cancer is primarily due to activation of NFkB p50 and p65 and the activating protein-1(AP-1) transcription factor heterodimer of JunD and Fra-1.These authors now show that inhibition of JunD in prostate cancer cells results in induction of the stress sensors Gadd45a and Gadd45g but not Gadd45b, which, in turn, leads to activation of c-Jun N-terminal kinase (JNK), ultimately resulting in prostate tumor cell death and inhibition of tumor development (Fig. I).