Role of IKKs and Transcription Factor NF-kB in Prostate Tumorigenesis
Abstract
One of the central anti-apoptotic pathways induced by diverse cellular stresses is mediated by NF-kappaB transcription factors. The overall aim of this project is to understand the role of up-stream IkappaB kinases and NF-kappaB 'survival signaling' pathway in tumorigenesis in prostate. During the current funding period we focused on NF-kappaB activity in normal prostate epithelial cells and in a panel of androgen-dependent and androgen-independent prostate carcinoma (PC) cell lines. Our results indicated that NF-KappaB was constitutively activated in human androgen-independent PC cell lines. We found that the level of IkappaB alpha phosphorylation and the rate of IkappaB alpha degradation were increased in PC cells with high constitutive NF-kappaB activity due to the constitutive activation of IKKs. We have developed a comprehensive picture of NP-kappaB induction in different prostate cell lines by diverse NF-kappaB activators. It appeared that in spite of the high constitutive level of NF-kappaB activity, NF-kappaB in general is readily inducible in PC cells. Results of our experiments also showed that selenium, which is an effective preventive agent for PC, inhibited IKK and NF-kappaB activity and induced apoptosis in PC cells. Next year we will study the role of specific IKKs in constitutive activation of NP-kappaB in PC cell lines and PC tumors.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2002
- Accession Number
- ADA405665
Entities
People
- Irina V. Budunova