The Role of NF-kB in Normal and Transformed Mammary Epithelium
Annual rept. 1 Aug 1998-31 Jul 1999
VANDERBILT UNIV MEDICAL CENTER NASHVILLE TN
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A knowledge of the molecular signaling pathways which when perturbed result in mammary cell transformation will provide us with information in the fight against human breast cancer. The NF-kB family of transcription factors are a major component of signal transduction pathways regulating cell proliferation, differentiation and death. We are investigating their role in the development of normal and transformed mammary epithelium. Our hypothesis is that expression of specific NF-kB factors is necessary for differentiation and maturation of mammary epithelium and that alteration in NF-kB factor expression can effect transformation. We have created lines of transgenic mice which perturb NF-kB levels by overexpression of the family member already suspected to be involved in carcinogenesis NFkB2 and of a dominant inhibitor of NF-kB activity IkBalpha-deltaN in the mammary gland. Transgene expression of both types has been confirmed at various stages during mammary development. This expression alters the profile of NF-kB activity during pregnancy and lactation. The downstream effects of such alterations are being characterized.
- Anatomy and Physiology
- Medicine and Medical Research