Molecular Mechanisms of Breast Cancer Progression: Lessons from Mouse Mammary Cancer Models and Gene Expression Profiling

The development of breast cancer is thought to occur through a multi-step process. The majority of breast cancers likely develop over extended periods of time arising from early, pre-invasive lesions such as atypical ductal hyperplasia (ADH) and carcinoma in situ (DCIS), progressing to invasive carcinoma and culminating in metastatic disease. However, the molecular mechanisms underlying this process are still poorly understood. The molecular analysis of this multi-step process in human patients is hampered by the difficulty in obtaining tissue samples at all tumor stages, especially from the same patient. In contrast, mouse models of mammary cancer progression are amenable to pathological, genetic and biochemical analyses at all tumor stages. Global gene expression profiling allows for simultaneous interrogation of the expression of thousands of genes and provides important opportunities to identify molecular signatures of tumor progression. This approach provides a means to define networks of cancer-related genes and their potential role in tumor progression. In this review, we discuss mouse models that have contributed substantially to understanding the molecular mechanisms of breast cancer progression and insights gained from gene expression profiling of mouse mammary cancer models and human breast cancer.