Nature and Prognostic Significance of Alterations in the DCC and E-Cadherin Genesin Breast Cancer

摘要

Breast cancer, like other epithelial tumors, is a highly complex and multi-factorial process. Oncogenes involved in metastasis represent a important area of exploration toward understanding the progression of this disease. This grant focuses on the role of Deleted in Colon Cancer (DCC) and E-cadherin. Ample evidence has been published implicating both in breast cancer. In the last year, we have concentrated on the regulation of expression of these molecules in breast cancer and the regulation of adhesion. Specifically, we have shown the E-cadherin promoter appears to be regulated by trans-activation, as opposed to methylation, and further localized regions of the promoter that are critical for expression. We have also shown the expression of E-cadherin protein is concordant with expression of alpha-catenin and beta-catenin, but not with p120ctn. Its expression is frequently altered, but rarely lost in breast ductal carcinoma, and not significantly associated with outcome. We have also examined expression of Met, the HGF/SF receptor in ductal carcinoma, since it is thought to be responsible for down-regulation of adhesion. We found overexpression of Met is a highly significant, independent predictor of decreased survival in the 20-25% of cases were it is expressed.