Analysis of the Regulation of Expression of Transforming Growth Factor-Beta in Human Breast Cancer Cells.
Annual rept. 1 Oct 96-30 Sep 97
DARTMOUTH COLL HANOVER NH
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This grant entails two objectives. The first objective derived from prior work which identified TGF-beta1 as an important cytokine in breast cancer. The specific goal of this objective was to identify the molecular mechanism of overexpression of TGF-beta1. We have analyzed paired normal and tumor specimens from patients and have determined that this genetic locus is not amplified in a significant proportion of patients. In other work we have recently obtained data which refutes the suggestion that overexpression of TGF-beta1 is associated with poor patient outcome. The second objective of the grant was to identify the molecular determinants of promoter usage for TGF-beta3 in breast cancer cell lines. In the past year we have focussed on examination of the methylation pattern at CpG sites in the vicinity of the two TGF-beta3 promoters. We have observed that whereas CpG sites closest to the breast cancer-specific downstream promoter are methylated in non breast cancer cells, they are unmethylated in breast cancer cells.
- Anatomy and Physiology