Expression of the Epidermal Growth Factor Receptor Family in Transgenic Mouse Models of Human Breast Cancer.

Abstract

Abstract : Transgenic mice expressing an activated neu oncogene in the mammary epithelium develop metastatic mammary tumors within a short latency period. Given our recent observations suggesting that co-activation of the epidermal growth factor receptor and Neu in the mammary epithelium of transgenic mice results in the synergistic transformation of the mammary epithelium, we decided to assess whether a functional EOFR was required for Neu-induced tumors. To accomplish this objective, we have recently interbred these activated Neu strains to a naturally occurring mouse mutation possessing a catalytic defective EGFR (Waved-2). The preliminary results of these analyses revealed that while a functionally active EOFR was not absolutely required for Neu induced tumorigenesis, inactivation of its catalytic activity appears to affect tumor growth rate. The observed cooperativity of EGFR and Neu may in part be due the ability of the EGFR and Neu to recruit distinct but complementary signaling pathways. In fact Neu can recruit the Src signaling pathway to EGFR/Neu complexes through a direct and specific binding to the catalytic domain of Neu. We are currently exploring the role of other EGFR family members in Neu mediated mammary tumors by crossing the MMTV/neu mice to the recently established MMTV/erbB-4 mice.