Growth Factors and Metalloproteinases in Breast Cancer Development and Progression.
Annual rept. 1 Sep 94-31 Aug 95,
VANDERBILT UNIV MEDICAL CENTER NASHVILLE TN
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The overall goal of this project is to test the hypothesis that the action of growth factors on mammary neoplasia and tumor progression is mediated, at least in part, by their action on the genes for matrix-degrading metalloproteinases MMPs. This hypothesis will be tested using transgenic mouse model systems of breast cancer. Initial studies involved the generation of transgenic mice expressing the MMP matrilysin under the control of the MTV promoterenhancer. One line of transgenic mice demonstrated the induction of an alveolar phenotype in virgin female mice similar to that observed in MMTV-TGFa transgenic mice. These results provide support for the initial hypothesis that TOFa may be affecting mammary gland development by enhancing MMP gene expression, although further confirmation of the results is required. These studies will assist in determining the most effective use of synthetic inhibitors of MMPs as potential therapeutic agents for the treatment of breast cancer.
- Anatomy and Physiology
- Metallurgy and Metallography