Non-Classical NF-kappaB Forms and Bcl-3 in Breast Cancer Development and Resistance to Cancer Therapy
Abstract
Breast cancer development is typified by the overexpression of growth factors and growth factor receptors, expression of cell cycle markers such as cyclin D1 and c-myc, expression of chemokines such as RANTES, and development of resistance to cancer therapies. We and others have provided evidence that the transcription factor NF-kappaB and associated activities are expressed/activated in human breast cancer. Specifically we found that the NF-kB2/p52 NF-kappaB subunit and Bcl-3 are expressed in a significant number of breast tumors. Our goals were to: (i) identify genes regulated by Her-2/neu and Bcl-3 that may be relevant to the progression of the disease, (ii) determine the mechanism whereby Bcl-3 blocks cancer-therapy induce apoptosis, and (iii) determine if Bcl-3 and the associated NF-kappaB subunit p52 are required for the development of experimental breast tumors in animal models. Our published results indicate that Bcl-3 expression suppresses p53 activation and promotes resistance to cancer therapies. Preliminary data indicate that Her-2/neu expression activates NF-kB through an Akt and IKK-dependent manner, and promotes phosphorylation of estrogen receptor (a potentially important mechanism for tamoxifen resistance and enhanced responses to estrogens).
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2006
- Accession Number
- ADA462855
Entities
People
- Albert S Baldwin
Organizations
- University of North Carolina at Chapel Hill