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| Subject Categories: Signal Transduction | Molecular Biology of Disease |
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| The EMBO Journal
(2008) 27, 910–920, doi:10.1038/emboj.2008.22 Published online 14 February 2008 |
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| ShcA signalling is essential for tumour progression in mouse models of human breast cancer |
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| Josie Ursini-Siegel1, W Rod Hardy2, Dongmei Zuo1, Sonya H L Lam1, Virginie Sanguin-Gendreau1, Robert D Cardiff3, Tony Pawson2 and William J Muller1 |
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1 Departments of Medicine and Biochemistry, McGill University, McGill University Health Center, Montreal, Quebec, Canada 2 Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada 3 Center for Comparative Medicine, University of California Davis, Davis, CA, USA To whom correspondence should be addressed William J Muller, Departments of Medicine and Biochemistry, McGill University, McGill University Health Center, 687 Pine Avenue West, Room H5-21, Montreal, CDN-Montreal, Quebec, Canada H3A 1A1. Tel.: +1 514 934 1934; ext. 36383; Fax: +1 514 843 1478; E-mail: william.muller@mcgill.ca Received 6 December 2007; Accepted 24 January 2008; Published online 14 February 2008. |
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| Abstract |
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| 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. |
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| Keywords: ErbB2, mammary tumorigenesis, MT, ShcA |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated RESEARCHShcA signalling is essential for tumour progression in mouse models of human breast cancer The EMBO Journal Article ShcA tyrosine phosphorylation sites can replace ShcA binding in signalling by middle T-antigen The EMBO Journal Article (15 Nov 2001) |
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