Temporal Control of Transforming Growth Factor (TGF) - Betal Expression on Mammary Cell Multistep Transformation
Abstract
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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2000
- Accession Number
- ADA390196
Entities
People
- C. L. Arteaga
- Nancy Dumont
Organizations
- Vanderbilt University Medical Center