Dysregulation of cellular signaling by HER2/neu in breast cancer

Abstract

Human epidermal growth factor receptor-2 (HER2/neu; erbB2) belongs to a family of four transmembrane receptor tyrosine kinases involved in signal transduction pathways that regulate cell growth and proliferation. Amplification or overexpression of HER2/neu occurs in about 30% of human breast and ovarian cancers and is associated with a poor clinical outcome, including short survival time and short time to relapse. Recent advances in our understanding of HER2/neu signaling pathways have greatly increased our knowledge of breast cancer tumorigenesis and have provided new targets for treating breast and ovarian tumors that overexpress HER2/neu. This review will focus on the signaling network mediated by HER2/neu in breast cancer and discuss our understanding of these pathways, which seem to be particularly important in mediating cell survival and growth under a wide variety of circumstances in breast cancer.