Reference SummaryAndrechek ER, Proc Natl Acad Sci U S A 2000 Mar 28;97(7):3444-9

Title

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

Authors

Andrechek ER; Hardy WR; Siegel PM; Rudnicki MA; Cardiff RD; Muller WJ

Journal

Proc Natl Acad Sci U S A

Volume

97

Issue

7

Year

2000

Pages

3444-9

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 lobulo-alveolar 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.

Links

J:61202 – MGI References
10716706 – National Library of Medicine/PubMed

Models

Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
STOCK Erbb2tm8(Erbb2)Mul/+ Tg(MMTV-cre)7Mul Mammary gland adenocarcinoma - comedo Mammary gland

45

STOCK Erbb2tm8(Erbb2)Mul/+ Tg(MMTV-cre)7Mul Mammary gland lesion Mammary gland

100

FVB/N-Tg(MMTV-cre)7Mul Mammary gland tumor Mammary gland

0

STOCK Erbb2tm8(Erbb2)Mul/+ Mammary gland tumor Mammary gland

0