The Role of I Kappa B Kinases in Prostate Carcinogenesis and the Effect oh 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 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 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 TMEFF2. 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 and important role for both IKKalpha and IKKbeta in development and progression of CaP. Therefore inhibition of either protein kinase ort both would be an effective and attractive option of the treatment of CaP.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2006
- Accession Number
- ADA452532
Entities
People
- Michael Karin
Organizations
- University of California, San Diego