Roles of IkB-a Protein Kinases in Activation of NF-kB in Breast Cancer
Abstract
We previously demonstrated that breast cancer cells constitutively express high levels of nuclear NF-kB/Rel, which correlated with decreased stability of IkB inhibitory proteins. Our objective is to elucidate the mechanisms leading to IkB turnover and thereby aberrant NF-kB activation in breast cancer. Activation of NF-kB has clearly been shown to be dependent upon the rate of IkB turnover which is regulated by 1) the two kinase components (IKK alpha and IKK beta) of the IkB kinase complex (IKK), and 2) the protein kinase CK2. The relative contribution of these kinases depends upon signal and cell context. We assessed the expression level and kinase activity of CK2 and the IKK alpha and IKK beta in human and mouse breast cancer cell lines, as well primary breast cancer specimens from patients and from transgenic mice. We also tested the hypothesis that CK2 and IKK kinases play an important role in the growth, survival and transformed phenotype of breast cancer cells through NF-kB activation. Overall, these studies should contribute to the understanding of the signaling mechanisms involved in the constitutive activation of NF-kB in mammary tumors and may help define novel therapeutic targets for the treatment of breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2003
- Accession Number
- ADA412856
Entities
People
- Raphaelle A. Romieu-mourez
Organizations
- Boston University Medical Campus