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ShcA signalling is essential for tumour progression in mouse models of human breast cancer
- Source :
- The EMBO Journal. 27:910-920
- Publication Year :
- 2008
- Publisher :
- Wiley, 2008.
-
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.
- 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
Subjects
Details
- ISSN :
- 14602075 and 02614189
- Volume :
- 27
- Database :
- OpenAIRE
- Journal :
- The EMBO Journal
- Accession number :
- edsair.doi.dedup.....e778e670558b17c0a50abb91dd006869