ShcA signalling is essential for tumour progression in mouse models of human breast cancer

Josie Ursini-Siegel, W. Rod Hardy, Dongmei Zuo, Sonya H.L. Lam, Virginie Sanguin-Gendreau, Robert Cardiff, Tony Pawson, William J. Muller

Research output: Contribution to journalArticle

96 Scopus citations

Abstract

To explore the in vivo significance of ShcA during mammary tumorigenesis, we used mice expressing several phosphotyrosine-deficient ShcA alleles under the control of their endogenous promoter. We show that all three ShcA tyrosine phosphorylation sites are involved in the early stages of mammary tumour progression, including loss of the myoepithelial cell layer surrounding hyperplasias and during progression to carcinoma. We have determined that signals emanating from Y313 are important for tumour cell survival, whereas Y239/240 transduce signals promoting tumour vascularization. We further demonstrate that loss of ShcA expression in mammary epithelial cells abrogates tumour development. This study is the first to directly demonstrate that signalling downstream from the ShcA adaptor protein is critical for breast cancer development.

Original languageEnglish (US)
Pages (from-to)910-920
Number of pages11
JournalEMBO Journal
Volume27
Issue number6
DOIs
StatePublished - Mar 19 2008

Keywords

  • ErbB2
  • Mammary tumorigenesis
  • MT
  • ShcA

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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    Ursini-Siegel, J., Hardy, W. R., Zuo, D., Lam, S. H. L., Sanguin-Gendreau, V., Cardiff, R., Pawson, T., & Muller, W. J. (2008). ShcA signalling is essential for tumour progression in mouse models of human breast cancer. EMBO Journal, 27(6), 910-920. https://doi.org/10.1038/emboj.2008.22