1. ShcA signalling is essential for tumour progression in mouse models of human breast cancer
- Author
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Dongmei Zuo, Sonya H.L. Lam, William J. Muller, Virginie Sanguin-Gendreau, Tony Pawson, Robert D. Cardiff, Josie Ursini-Siegel, and W. Rod Hardy
- Subjects
Lung Neoplasms ,Src Homology 2 Domain-Containing, Transforming Protein 1 ,Breast Neoplasms ,Endogeny ,Biology ,Article ,General Biochemistry, Genetics and Molecular Biology ,Mice ,chemistry.chemical_compound ,medicine ,Animals ,Humans ,Phosphorylation ,Tyrosine ,Molecular Biology ,Adaptor Proteins, Signal Transducing ,General Immunology and Microbiology ,General Neuroscience ,Myoepithelial cell ,Mammary Neoplasms, Experimental ,Cancer ,Signal transducing adaptor protein ,Tyrosine phosphorylation ,medicine.disease ,Shc Signaling Adaptor Proteins ,chemistry ,Immunology ,Disease Progression ,Cancer research ,Female ,Signal transduction ,Signal Transduction - 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.
- Published
- 2008