Expression of activated oncogenes in the murine mammary gland: transgenic models for human breast cancer

Abstract

Breast cancer is the leading cause of death among non-smoking women and thus has been the focus of intensive research. It has been generally accepted that the deregulation of oncogenes or their regulators play a pivotal role in progression of this prevalent disease. For example, amplification and overexpression of a number of oncogenes has been observed in a proportion of primary breast cancer biopsies. More recently, there has also been reports of inactivation tumor suppressor genes in human breast cancer. While there is compelling evidence for a role of these genes in breast cancer tumor progression due to limitations inherent in these studies it is difficult to establish a direct causal association between expression of a certain oncogene and tumor progression. For this reason many groups have employed the transgenic mouse as a model system to directly study effects of oncogene expression in the murine mammary gland. This review will attempt to highlight some of the important lessons and potential applications that have emerged from the study of oncogene expression in the mammary epithelium of transgenic mice. The utility of the transgenic system to assess the transforming potential of oncogenes, to investigate the multi-step nature of malignant progression, and to be used as models for therapeutic intervention will be discussed.