Cited by 230HER2/EGFR in Cancer ResearchBreast Lesions and CarcinomasCancer-related Molecular Pathways

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

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Andrechek, Eran R., Hardy, William R., Siegel, Peter M., Rudnicki, Michael A., Cardiff, Robert D., Muller, William J.·2000·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.97.7.3444PMC PMC16259

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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 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.

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Authors: Andrechek, E. R., Hardy, W. R., Siegel, P. M., Rudnicki, M. A., Cardiff, R. D., & Muller, W. J.
Affiliations: University of California, Davis (US)
ORCID: Andrechek, Eran R.
Hardy, William R.
Siegel, Peter M.
Rudnicki, Michael A.
Cardiff, Robert D.
Muller, William J.
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 2000-03-14
Volume: 97
Issue: 7
Pages: 3444-3449
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.97.7.3444
PMC: PMC16259
OpenAlex: W2041576667
Cited by: 230
References: 38
Citations by year: 2026: 5 · 2025: 4 · 2024: 5 · 2023: 7 · 2022: 2 · 2021: 6 · 2020: 10 · 2019: 7 · 2018: 6 · 2017: 7 · 2016: 8 · 2015: 9 · 2014: 12 · 2013: 9 · 2012: 8
FWCI: 5.59
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Cancer Institute (U01CA105490)
Topics: Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
Health Sciences › Medicine › Pathology and Forensic Medicine › Breast Lesions and Carcinomas
Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Keywords: neu oncogene, c-erbB-2, HER2, gene amplification, mammary carcinogenesis, transgenic mouse model, conditional gene expression, endogenous promoter, breast cancer, oncogene overexpression
MeSH terms: Animals, Disease Models, Animal, Gene Amplification, Humans, Immunohistochemistry, Mammary Neoplasms, Experimental, Mice, Transgenic, DNA, Complementary, Genes, erbB-2, Mice

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

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