Role of IKKs and Transcription Factor NF-kB in Prostate Tumorigenesis
Abstract
The goal of this project is to understand the role of IKK kinases and NF-kappa B "survival signaling" pathway in tumorigenesis in prostate. In our previous studies we found that NF-kappa B was constitutively activated in human androgen-independent prostate carcinoma (PC) cell lines. During the current findings period we found that one of the IKKs, IKK epsilon was only expressed in androgen-independent PC cells with high level of constitutively active NF-kappa B. We obtained experimental evidence that IKK epsilon could be involved in the NF-kappa B induction in PC cells through a positive feedback loop. We also found that the conditioned medium from PC cells induced NF-kappa B in cells with low level of NF-kappa B activity through secreted proteinaceous factor. These data strongly suggest that NF-kappa B activity in androgen-independent PC cells may be mediated through an autocrine/paracrine loops. We have generated 175 clones of PC cells transfected with d.n. mutants of different IKKs. We have assessed the effect of d.n. IKK mutants on NF-kappa B in clones with the highest level of d.n. IKK expression. The IKK alpha did not significantly affect NF-kappa B function in PC cells; IKK epsilon d.n. mutant moderately affected NF-kappa B activation by selective NF-,kappa B inducers; IKK beta and IKK gamma mutants significantly blocked transcriptional activity of NF-kappa B in PC cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2003
- Accession Number
- ADA417764
Entities
People
- Irina V. Budunova