Temporal Control of Transforming Growth Factor (TGF) - Betal Expression on Mammary Cell Multistep Transformation
Annual summary rept. 1 Oct 1999-30 Sep 2000
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 autocrine TGF-beta signaling promotes mammary carcinogenesis. There is also evidence that tumor cell TGF-betas are involved in tumor maintenance and progression by promoting epithelial to mesenchymal transition of epithelial cancer cells, and by modulating tumor-host interactions that are critical for cancer cell survival. The objective of this proposal is to generate a transgenic breast tumor model in which the mammary epithelial expression of TGF-beta 1 can be temporally regulated to understand the role of this molecule in progressive sequential stages of mammary neoplasia. In addition, by expressing a dominant negative type II TGF-beta dnT-betaRII in MDA-23l human breast cancer cells, we will determine whether blocking autocrine TGF-beta in these cells affects their invasive metastatic phenotype in vitro and in vivo. Results to date indicate that the basal migratory potential of dnT-betaRII expressing cells is impaired, suggesting that their invasive phenotype may indeed be affected by blocking autocrine TGF-beta signaling.
- Anatomy and Physiology
- Medicine and Medical Research