Inflammation in Prostate Carcinogenesis: Role of the Tumor Suppressor Par-4
Final rept. 1 Jul 2009-31 Aug 2012
SANFORD-BURNHAM MEDICAL RESEARCH INST LA JOLLA CA
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Prostate cancer PCa is one of the most common malignancies in men, and is a complex disease in its development and response to therapy. Loss of tumor suppressors genes is a frequent initiating event that is irreversible, whereas tumor promotion and progression are susceptible to modulation, which provides a rationale for therapeutic intervention. Tumor promotion is highly regulated by the interaction between initiated cells and their microenviroment and inflammation is a frequent and important tumor promoter. However, despite the strong evidence for an inflammatory component to the pathology of PCa, the process of inflammation and the related signaling pathways are largely unknown. Therefore, a better understanding of the molecular mechanisms that govern the inflammatory response and its impact on PCa progression is of paramount importance in developing novel therapies for PCa. Here we report the identification of a novel network between tumor suppressors Par-4, PKCzeta and PTEN and the characterization of the inflammatory response unleashed upon their loss. Importantly, our results also demonstrate that inflammation is not only secondarily associated to carcinogenesis but it is an important contributing factor in tumor promotion.
- Medicine and Medical Research