Active signaling by Neu in transgenic mice

M. P. DiGiovanna, M. A. Lerman, R. J. Coffey, W. J. Muller, Robert Cardiff, D. F. Stern

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Transgenic mice engineered to overexpress the HER-2/neu/erbB-2 protooncogene under the control of a mammary-specific promoter develop mammary tumors and are a model for human breast cancer. Signal transduction by Neu was examined in situ in the tumors of these transgenic mice. This was accomplished using the PN2A monoclonal antibody, which recognizes Neu only in the phosphorylated, and therefore actively signaling, state. Immunohistochemistry using PN2A demonstrated that Neu actively signals in the tumors of Neu transgenic mice. Expression of Neu was always accompanied by co-overexpression of the endogenous epidermal growth factor receptor. Qualitatively similar results were found in mammary tumors from mice bitransgenic for the neu and transforming growth factor-α genes (both driven by the mouse mammary tumor virus promoter). Early mammary lesions demonstrated distinctive patterns of Neu activation relative to expression levels. Overexpression and activation were separable both temporally and spatially. These results refine the multi-step model for the role of Neu in mammary neoplasia and establish phosphorylation-state specific antibodies as a powerful tool for investigating tumor progression.

Original languageEnglish (US)
Pages (from-to)1877-1884
Number of pages8
JournalOncogene
Volume17
Issue number14
DOIs
StatePublished - Oct 8 1998

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Transgenic Mice
Breast
Breast Neoplasms
Neoplasms
Phospho-Specific Antibodies
Mouse mammary tumor virus
Transforming Growth Factors
Epidermal Growth Factor Receptor
Carcinogens
Signal Transduction
Immunohistochemistry
Monoclonal Antibodies
Genes

Keywords

  • Activation
  • Breast cancer
  • HER-2/Neu/ErbB-2
  • Phosphorylation
  • Transforming growth factor-alpha (TGFα)
  • Transgenic mice

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

DiGiovanna, M. P., Lerman, M. A., Coffey, R. J., Muller, W. J., Cardiff, R., & Stern, D. F. (1998). Active signaling by Neu in transgenic mice. Oncogene, 17(14), 1877-1884. https://doi.org/10.1038/sj.onc.1202091

Active signaling by Neu in transgenic mice. / DiGiovanna, M. P.; Lerman, M. A.; Coffey, R. J.; Muller, W. J.; Cardiff, Robert; Stern, D. F.

In: Oncogene, Vol. 17, No. 14, 08.10.1998, p. 1877-1884.

Research output: Contribution to journalArticle

DiGiovanna, MP, Lerman, MA, Coffey, RJ, Muller, WJ, Cardiff, R & Stern, DF 1998, 'Active signaling by Neu in transgenic mice', Oncogene, vol. 17, no. 14, pp. 1877-1884. https://doi.org/10.1038/sj.onc.1202091
DiGiovanna MP, Lerman MA, Coffey RJ, Muller WJ, Cardiff R, Stern DF. Active signaling by Neu in transgenic mice. Oncogene. 1998 Oct 8;17(14):1877-1884. https://doi.org/10.1038/sj.onc.1202091
DiGiovanna, M. P. ; Lerman, M. A. ; Coffey, R. J. ; Muller, W. J. ; Cardiff, Robert ; Stern, D. F. / Active signaling by Neu in transgenic mice. In: Oncogene. 1998 ; Vol. 17, No. 14. pp. 1877-1884.
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