Analysis of the Regulation of Expression of Transforming Growth Factor-Beta in Human Breast Cancer Cells
Abstract
This combined report of research and career development grants entails three objectives. Progress on the first objective this year centered on an analysis of the importance of a functionally intact TGF-beta signaling pathway with regards to tumor necrosis factor (TNF)-mediated cytotoxicity of MCF-7 cells. We have documented that loss of TGF-beta responsiveness resulted in increased Bcl-2 levels and marked resistance to TNF. The second objective of the grant was to evaluate the in vivo tumorigenicity and metastatic potential of breast cancer cells altered with regard to their production of and responsiveness to TGF-beta. Those experiments are still underway, and no conclusion has been reached. The third objective was to identify the molecular determinants of promoter usage for TCF-beta-3 in breast cancer cell lines. In the past year we have observed that whereas CpG sites closest to the breast cancer-specific downstream promoter are nearly completely methylated in non breast cancer cells, they are mostly unmethylated in breast cancer cells. This is consistent with the observed expression pattern of these cells, and suggests that CpG methylation is the basis of this difference.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1998
- Accession Number
- ADA369254
Entities
People
- Bradley A. Arrick
Organizations
- Dartmouth College