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PMID: 18273058 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

The EMBO journal ·Vol. 27 ·No. 6 ·2008-03-19 ·Pages 910-20

Ursini-Siegel J, Hardy WR, Zuo D, Lam SH, Sanguin-Gendreau V, Cardiff RD, Pawson T, Muller WJ

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.

MeSH Terms
Adaptor Proteins, Signal Transducing/physiology Animals Breast Neoplasms/metabolism,pathology Disease Progression Female Humans Lung Neoplasms/metabolism,pathology,secondary Mammary Neoplasms, Experimental/metabolism,pathology Mice Phosphorylation Shc Signaling Adaptor Proteins Signal Transduction/physiology Src Homology 2 Domain-Containing, Transforming Protein 1 Tyrosine/metabolism
Chemicals
Adaptor Proteins, Signal Transducing SHC1 protein, human Shc Signaling Adaptor Proteins Shc1 protein, mouse Src Homology 2 Domain-Containing, Transforming Protein 1 Tyrosine
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Ursini-Siegel Josie
Department of Medicine, McGill University, McGill University Health Center, Montreal, Quebec, Canada.
Hardy W Rod
Zuo Dongmei
Lam Sonya H L
Sanguin-Gendreau Virginie
Cardiff Robert D
Pawson Tony
Muller William J
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
1460-2075
DOI
10.1038/emboj.2008.22
Published
2008-03-19
Epub
2008-00-14
Pages
910-20
Language
English
Region
England
NLM ID
8208664
PMCID
PMC2274931
Subset
IM
External Links
PubMed source DOI: 10.1038/emboj.2008.22 PMC Full Text View journal details
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