Gene expression profiling of neu-induced mammary tumors from transgenic mice reveals genetic and morphological similarities to ErbB2-expressing human breast cancers

Eran R. Andrechek, Michael A. Laing, Adele A. Girgis-Gabardo, Peter M. Siegel, Robert Cardiff, William J. Muller

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Numerous studies have shown that the overexpression and amplification of ErbB2/Neu are observed in 20-30% of patients afflicted with breast cancer. Furthermore, it has also been observed that the elevated expression of ErbB2/ Neu also correlates with poor prognosis and clinical outcome. Given the prevalence of this disease, we sought to create mouse models that mimic the human condition. In this study, we compared two mouse models expressing activated neu under the control of the endogenous and mouse mammary tumor virus promoters. Although histologically similar, the latency and metastatic potential of these tumors are remarkably different. Gene expression profiling of tumor RNA from the two Neu mouse models revealed distinctive and nonoverlapping patterns of gene expression. Consistent with noninvasive nature of the mammary tumors induced by expression of neu under the endogenous promoter, these tumors expressed a number of markers characteristic of a highly differentiated state. In addition to these differences, these analyses revealed that in contrast to the mouse mammary tumor virus-based Neu model, the endogenous promoter tumors expressed elevated levels of two genes (Grb7 and Cab1) that are closely linked to ErbB2 and often coamplified in noninvasive ductal carcinoma in situ. Furthermore, this analysis has revealed several transcription factors that may be involved in ErbB2-mediated tumorigenesis. Taken together, these results illustrate the similarity of the endogenously regulated Neu tumor model to the human disease.

Original languageEnglish (US)
Pages (from-to)4920-4926
Number of pages7
JournalCancer Research
Volume63
Issue number16
StatePublished - Aug 15 2003

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Gene Expression Profiling
Carcinogens
Transgenic Mice
Mouse mammary tumor virus
Breast Neoplasms
Neoplasms
Carcinoma, Intraductal, Noninfiltrating
Carcinogenesis
Transcription Factors
RNA
Gene Expression
Genes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Gene expression profiling of neu-induced mammary tumors from transgenic mice reveals genetic and morphological similarities to ErbB2-expressing human breast cancers. / Andrechek, Eran R.; Laing, Michael A.; Girgis-Gabardo, Adele A.; Siegel, Peter M.; Cardiff, Robert; Muller, William J.

In: Cancer Research, Vol. 63, No. 16, 15.08.2003, p. 4920-4926.

Research output: Contribution to journalArticle

Andrechek, Eran R. ; Laing, Michael A. ; Girgis-Gabardo, Adele A. ; Siegel, Peter M. ; Cardiff, Robert ; Muller, William J. / Gene expression profiling of neu-induced mammary tumors from transgenic mice reveals genetic and morphological similarities to ErbB2-expressing human breast cancers. In: Cancer Research. 2003 ; Vol. 63, No. 16. pp. 4920-4926.
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