The Roles of Ik(Beta) Kinases in Prostate Carcinogenesis and the Effect of Their Inhibition on Survival of Prostate Tumors

Abstract : 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 IKK(beta) or the IKK(alpha) subunit of IKK are deleted or inhibited in prostate epithelial cells. We found that neither IKK(beta) nor IKK(alpha) are required for normal prostate development, however IKK(alpha) may play an important role in the development of advanced CaP. The study on the role of IKK(beta) in prostate carcinogenesis in animal models is ongoing. We also found that IKK/NF-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 IKK/NF-kB in CaP development and progression is currently underway, our results obtained during last year suggest an important role for both IKK(alpha and IKK(beta) 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.