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A Role for the NF-kb/Rel Transcription Factors in Human Breast Cancer
Final rept. 1 Jul 94-30 Jun 98
NORTH CAROLINA UNIV AT CHAPEL HILL
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Human breast cancer is characterized by the inappropriate expression of growth factors, kinases and possibly certain transcription factors Our project has focused on the regulation of the NF-kB family of transcription factors in human breast cancer. Additionally, the project has analyzed a role for the VNTR elements in the hereditary susceptibility of women to breast cancer. We have found that NF-kB is activated in virtually all breast cancers. Interestingly, the form of NF-kB that is activated is not the classic form of NF-kB the p5Op65 heterodimer but rather involves the activation of the p52 form of NF-kB along with c-Rel and the IkB homolog Bcl-3. Additionally, our work revealed that NF-kB suppresses transformation associated apoptosis and apoptosis induced by chemotherapy and radiation. We have identified a DNA binding activity that binds to the VNTR element. The possible association of the tumor suppressor protein p53 with this element is currently being explored. Furthermore, our data indicate that African-American and white controls differed in the normal spectrum of VNTR alleles. Rare alleles were significantly associated with breast cancer in African-American women, but not in white women.
APPROVED FOR PUBLIC RELEASE