Characterization of a Novel Intracellular Receptor for Phorbol Esters and Diacylglycerol in Prostate Cancer
Annual summary 1 Feb 2004-31 Jan 2006
PENNSYLVANIA UNIV PHILADELPHIA
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The small GTP-binding protein Rae controls essential functions, including actin cytoskeleton reorganization, cell proliferation, cell cycle progression, adhesion, migration and invasion. The relationship of Rae to prostate carcinogenesis has not been extensively studied. However upstream activators of Rae have been described to be hyperactivated in prostate cancer, and it is well known that growth factors are very important in the control of prostate cancer proliferation and progression, as well as in the maintenance of growth during androgen independency. Chimaerins, through their Rae-GAP activity, accelerate the hydrolysis of GTP from Rae, leading to its inactivation. To date four chimaerin isoforms have been isolated and reported alpha1, alpha2-, beta1- and beta2-Chimaerin. While 01- and beta1-chimaerin are restricted to brain and testis, respectively, alpha2- and beta2-chimaerin are widely expressed. No experimental information has been reported about the possible role of chimaerins in prostate cancer. Likewise, there are no information available about the expression of different chimaerin in prostate cancer cell lines. Our work hypothesis is that by inhibiting Rae function in prostate cancer cells, chimaerins will impair proliferation and reduce the invasive properties of prostate cancer cells.
- Anatomy and Physiology
- Medicine and Medical Research