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

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.

SUBMITTER: Ursini-Siegel J

PROVIDER: S-EPMC2274931 | biostudies-literature | 2008 Mar

REPOSITORIES: biostudies-literature

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

Ursini-Siegel Josie J Hardy W Rod WR Zuo Dongmei D Lam Sonya H L SH Sanguin-Gendreau Virginie V Cardiff Robert D RD Pawson Tony T Muller William J WJ

The EMBO journal 20080214 6

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 tumou ...[more]

PMID: 18273058

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