Transgenic Analysis of the Role of Transcription Factor AP-2 in Breast Development and Breast Cancer

摘要

Proto-oncogene c-erbB-2 is overexpressed in 25-30% human breast cancers. Recently, in vitro studies have shown that transcription factor AP-2 proteins can bind to a critical region in the c-erbB-2 promoter and activates the promoter. We have therefore begun to determine the role of AP-2 both in normal mammary gland development and in breast cancer. Analysis of human breast cancer biopsies reveals that there is a significant increase in AP-2 protein expression in the progression from benign breast epithelium. Moreover, the presence of various AP-2 family members correlates with the expression of important signal transduction molecules including c- erbB-2, ER and IGF-IR. To test the role of AP-2 alpha in the development of the mammary gland, We have generated transgenic mice with overexpression of either the wild-type or the dominant-negative forms of AP-2 alpha in the mammary gland.