Essential Role of T-Cell Factor/B-Catenin in Regulation of Rad6B: A Potential Mechanism for Rad6B Overexpression in Breast Cancer Cells

We have previously shown that the postreplication DNA repair gene Rad6B plays a critical role in the maintenance of genomic integrity of human breast cells. Whereas normal breast cells express low levels of Rad6B, increases in Rad6B expression occur in hyperplasia with overexpression in breast carcinomas. Here, we show that the human Rad6B gene is a transcriptional target of T-cell factor (TCF)-4/B-catenin/ p300. Rad6B promoter activity is subject to negative regulation in normal human MCF10A breast cells whereas it is constitutively active in metastatic MDA-MB-231 breast cancer cells. Derepression and activation of Rad6B promoter in MCF10A cells require coexpression of B-catenin and p300. Usin