ErbB2 overexpression in p53-inactivated mammary epithelial cells

Functional loss of p53 and ErbB2 overexpression are the frequent genetic alterations in human breast carcinomas. Here, we found that ErbB2 expression was upregulated in primary cultured mammary epithelial cells (MECs) isolated from mice with a defect in exons 5 and 6 of the p53 gene (p53(Delta 5,6)). The reporter gene activity in the p53(Delta 5,6) MECs transfected with the -756 bp flanking region of the hErbB2 gene was higher than the wild type MECs. p53 inactivation selectively increased the level of AP-2 alpha, but not AP-2 beta and AP-2 gamma and a mutation of the two AP-2 binding sites completely inhibited the reporter activity. (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.