The Genetic Analysis of the Role of Neu Differentiation Factor (Heregulin) in Neu-Induced Mammary Carcinomas in the Mouse..
Annual rept. 15 Jul 96-14 Jul 97
YALE UNIV NEW HAVEN CT
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We have examined the possible role of neu differentiation factor NDF in mammary tumongenesis using transgenic mice. NDF is a ligand for ErbB4, a member of the ErbB family of tyrosine kinase receptors, of which two other members EGFR and NEU have been implicated in human breast cancer. Transgenic mice expressing a chimeric ligand having an NDFb-derived receptor binding domain within a TGFa backbone under an MMTV promote developed Harderian gland hyperplasias at high frequency. One mouse of 18 founders developed mammary carcinoma. Neither phenotype was transmissible to offspring. Other constructs, including NDFb2A, and mutant derived from that isoform, failed to express at significant levels in transgenic mice, precluding further analysis. In a separate Task, we attempted to identify genes that cooperate with c-neu in mammary tumorigenesis by proviral tagging using MMTV that is passed from female C3H mice to offspring via their milk. However, the strain of C3H that we used has experienced phenotypic drift since its original derivation, and was found to have a very low incidence of mammary carcinoma for reasons that are not entrely clear. We did find evidence suggesting the presence of modifier loci in the FVB andor C3H strains that influence the latency of neu-induced mammary tumors.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research