Expression of the Epidermal Growth Factor Receptor Family in Transgenic Mouse Models of Human Breast Cancer.
Final rept. 1 Aug 94-31 Jul 98
MCMASTER UNIV HAMILTON (ONTARIO)
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Elevated expression of members of the epidermal growth factor receptor EGFR family has been frequently observed in a large number of sporadic breast cancers. For example, overexpression and amplification of the NeuErbB-2 protooncogene has been implicated as an important determinant in the initiation and progression of human breast cancer. To directly test the importance of the Neu in mammary tumor progression, we have derived transgenic mice that express Neu under the transcriptional control of the mouse mammary tumor virus MMTV promoterenhancer. The induction of mammary tumors in these strains was further correlated with elevated expression of ErbB-3 EGFR family member. To explore whether the catalytic activity of the EGFR is required for the induction of mammary tumors in these Neu strains, we have crossed the Neu transgenic mice with the Waved-2 strain which encode a catalytically inactive EGFR. The results of this cross revealed that the catalytic activity of EGFR is dispensable for Neu tumorigenesis. Taken together these observations argue that ErbB-3 and Neu are the principle EGFR family members involved in the induction of mammary carcinoma. We are currently testing the importance of erbB-3 in mammary tumorigenesis by interbreeding MMTVerbB-3 strains with the MMTVNeu strains.
- Anatomy and Physiology
- Medicine and Medical Research