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Mouse Models of Breast Cancer Progression.

The progression of the primary mammary epithelial cell to malignant phenotype involves multiple genetic events including the activation of dominant activating oncogenes and inactivation of specific tumour suppressor genes. Our laboratory has focused on the role of a class of receptor tyrosine kinases known as the epidermal growth factor receptor (EGFR) family in the induction of breast cancer. Elevated expression of the various EGFR family members has been observed in a large proportion of sporadic breast cancers and their derived cell lines. For example, amplification and overexpression of聽erbB-2/neu聽proto-oncogene is observed in 20-30% human breast cancer and is inversely correlated with the survival of the patient.

The major focus of our laboratory is to determine the relative contribution of the various EGFR family members and their coupled signaling pathways in ErbB-2 induced mammary tumour progression. Given the fact that germline inactivation of these signaling pathways results in either embryonic or perinatal lethality, we have used use Cre/Lox recombination system to specifically inactivate each of these signaling molecules members in the mammary epithelium of mice expressing activated聽erbB-2.

The results of these biochemical and genetic analyses will provide important insight in molecular basis for erbB-2 induced tumorigenesis and metastasis