The Roles of Ik(Beta) Kinases in Prostate Carcinogenesis and the Effect of Their Inhibition on Survival of Prostate Tumors
Annual rept. 1 Jan-31 Dec 2004
CALIFORNIA UNIV SAN DIEGO LA JOLLA
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This research project investigates the role of the IkB kinase IKK and NF-kB in the development of prostate cancer CaP, and examines the possibility that IKK inhibitors can be used in CaP treatment. To reach this goal we are employing two mouse models in which either the IKKbeta or the IKKalpha subunit of IKK are deleted or inhibited in prostate epithelial cells. We found that neither IKKbeta nor IKKalpha are required for normal prostate development, however IKKalpha may play an important role in the development of advanced CaP. The study on the role of IKKbeta in prostate carcinogenesis in animal models is ongoing. We also found that IKKNF-kB activities were increased during the evolution of androgen-independent CaP, a response that could be mediated by some of androgen-regulated genes, such as TMFF2. Furthermore, we found that a prototypical IKK inhibitor IT-3 can suppress the proliferation of human CaP cells. Although a more thorough examination of the role of IKKNF-kB in CaP development and progression is currently underway, our results obtained during last year suggest an important role for both IKKalpha and IKKbeta in development and progression of CaP. Therefore inhibition of either protein kinase or both would be an effective and attractive option for the treatment of CaP.
- Anatomy and Physiology
- Medicine and Medical Research