Temporal Control of Transforming Growth Factor (TGF) - Betal Expression on Mammary Cell Multistep Transformation
Annual rept. 1 Oct 1998-30 Sep 1999
VANDERBILT UNIV MEDICAL CENTER NASHVILLE TN
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The transforming growth factor TGF Betas are multifunctional polypeptide growth factors which potently inhibit the proliferation of mammary epithelial cells. There is evidence that loss of autocrine regulatory TGFbeta signaling promotes mammary carcinogenesis. There is also evidence that tumor cell TGFBetas are involved in tumor maintenance and progression by modulating tumor-host interactions that are critical for cancer cell survival, and also by promoting epithelial to mesenchymal transition of epithelial cancer cells. The objective of this proposal is to generate a transgenic breast tumor model in which the mammary epithelial expression of TGFbeta can be temporally regulated to understand the role of this molecule in progressive sequential stages of mammary neoplasia. In addition, by expressing dominant negative type II TGFbeta receptors in MDA-23l human breast cancer cells, we will determine whether blocking autocrine TGFbeta in these cells affects their invasive metastatic phenotype in vitro and in vivo.
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