The Role of Id Proteins in Breast Cancer
Abstract
E2A gene products (E47 and E12) are potent transcription factors containing the basic helix-loop-helix (bHLH) domain for DNA binding and dimerization. E2A proteins are thought to control cell growth and differentiation. E2A is also implicated to have a role as a tumor suppressor. E2A function can be inhibited by a group of inhibitors called Id. Thus, overexpression of Id proteins could diminish the function of E2A as a tumor suppressor, and potentially cause breast cancer. To test this hypothesis, we have generated transgenic mice expressing Id-1 in mammary epithelial cells, but have not detected any tumor formation. On the other hand, we have found Id-I overexpression in a large fraction of archived human breast cancer samples. The significance of Id-I overexpression in human breast cancer remains to be understood. Additionally, we have shown that E2A proteins in primary mammary epithelial cells and in the MDA-MB-231 breast cancer cell line are degraded through a proteasome mediated pathway. Furthermore, activation of the Notch signaling pathway has been found to accelerate the degradation of E2A proteins. The molecular mechanism underlying Notch-mediated degradation has been investigated. It is therefore possible that activation of Notch signaling pathway associated with mammary tumor formation may involve the elimination of E2A proteins, the putative tumor suppressors.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 01, 2001
- Accession Number
- ADA404876
Entities
People
- Sun Xiao-hong
Organizations
- Oklahoma Medical Research Foundation