Amplification of the neu/erbB-2 oncogene in a mouse model of mammary tumorigenesis

Eran R. Andrechek, William R. Hardy, Peter M. Siegel, Michael A. Rudnicki, Robert Cardiff, William J. Muller

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Abstract

The neu (c-erbB-2, Her-2) protooncogene is amplified and overexpressed in 20-30% of human breast cancers. Although transgenic mouse models have illustrated the role of Neu in the induction of mammary tumors, Neu expression in these models is driven by a strong viral promoter of questionable relevance to the human disease. To ascertain whether expression of activated Neu under the control of the endogenous promoter in the mammary gland could induce mammary tumors we have generated mice that conditionally express activated Neu under the transcriptional control of the intact endogenous Neu promoter. Expression of oncogenic neu in the mammary gland resulted in accelerated lobuloalveolar development and formation of focal mammary tumors after a long latency period. However, expression of activated Neu under the normal transcriptional control of the endogenous promoter was not sufficient for the initiation of mammary carcinogenesis. Strikingly, all mammary tumors bear amplified copies (2-22 copies) of the activated neu allele relative to the wild-type allele and express highly elevated levels of neu transcript and protein. Thus, like human erbB-2-positive breast tumors, mammary tumorigenesis in this mouse model requires the amplification and commensurate elevated expression of the neu gene.

Original languageEnglish (US)
Pages (from-to)3444-3449
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume97
Issue number7
DOIs
StatePublished - Mar 28 2000

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