Expression of the neu protooncogene in the mammary epithelium of transgenic mice induces metastatic disease

C. T. Guy, M. A. Webster, M. Schaller, T. J. Parsons, Robert Cardiff, W. J. Muller

Research output: Contribution to journalArticle

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Abstract

Overexpression and amplification of the neu (c-erbB2, ERBB2) protooncogene have been implicated in the development of aggressive human breast cancer. To directly assess the effect of mammary gland-specific expression of the neu protooncogene, transgenic mice carrying unactivated neu under the transcriptional control of the mouse mammary tumor virus promoter/enhancer were established. By contrast to the rapid tumor progression observed in several transgenic strains carrying the activated neu transgene, expression of unactivated neu in the mammary epithelium resulted in the development of focal mammary tumors after long latency. The majority of the mammary tumors analyzed expressed elevated levels of neu-encoded mRNA and protein. Overexpression of neu in the mammary tumors was also associated with elevated neu intrinsic tyrosine kinase activity and the de novo tyrosine phosphorylation of several cellular proteins. Interestingly, many of the tumor-bearing transgenic mice developed secondary metastatic tumors in the lung. These observations suggest that overexpression of the unactivated neu protein can induce metastatic disease after long latency.

Original languageEnglish (US)
Pages (from-to)10578-10582
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume89
Issue number22
DOIs
StatePublished - Nov 26 1992
Externally publishedYes

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Transgenic Mice
Breast
Epithelium
Breast Neoplasms
Mouse mammary tumor virus
Neoplasms
Proteins
Human Development
Human Mammary Glands
Transgenes
Carcinogens
Protein-Tyrosine Kinases
Tyrosine
Phosphorylation
Lung
Messenger RNA

Keywords

  • cancer metastasis
  • mammary tumorigenesis
  • protein-tyrosine kinase

ASJC Scopus subject areas

  • General

Cite this

Expression of the neu protooncogene in the mammary epithelium of transgenic mice induces metastatic disease. / Guy, C. T.; Webster, M. A.; Schaller, M.; Parsons, T. J.; Cardiff, Robert; Muller, W. J.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 89, No. 22, 26.11.1992, p. 10578-10582.

Research output: Contribution to journalArticle

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AU - Webster, M. A.

AU - Schaller, M.

AU - Parsons, T. J.

AU - Cardiff, Robert

AU - Muller, W. J.

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AB - Overexpression and amplification of the neu (c-erbB2, ERBB2) protooncogene have been implicated in the development of aggressive human breast cancer. To directly assess the effect of mammary gland-specific expression of the neu protooncogene, transgenic mice carrying unactivated neu under the transcriptional control of the mouse mammary tumor virus promoter/enhancer were established. By contrast to the rapid tumor progression observed in several transgenic strains carrying the activated neu transgene, expression of unactivated neu in the mammary epithelium resulted in the development of focal mammary tumors after long latency. The majority of the mammary tumors analyzed expressed elevated levels of neu-encoded mRNA and protein. Overexpression of neu in the mammary tumors was also associated with elevated neu intrinsic tyrosine kinase activity and the de novo tyrosine phosphorylation of several cellular proteins. Interestingly, many of the tumor-bearing transgenic mice developed secondary metastatic tumors in the lung. These observations suggest that overexpression of the unactivated neu protein can induce metastatic disease after long latency.

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