Non-Classical NF-KappaB Forms and Bc1-3 in Breast Cancer Development and Resistance to Cancer Therapy

摘要

Breast cancer development 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. Other 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. These goals may provide significant new insight into breast cancer progression and treatment.