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SHP2 is up-regulated in breast cancer cells and in infiltrating ductal carcinoma of the breast, implying its involvement in breast oncogenesis

Authors


Y M Agazie, Department of Biochemistry and Molecular Pharmacology and the Marry Babb Randolph Cancer Center, West Virginia University, Morgantown, WV 26506, USA. e-mail: yagazie@hsc.wvu.edu

Abstract

Aims:  To determine whether Src homology phosphotyrosyl phosphatase 2 (SHP2) is up-regulated in breast cancer and, if so, to determine whether its up-regulation has any relationship with clinical variables of breast cancer.

Methods and results:  Immunoblotting, immunohistochemistry and immunofluorescence microscopy were used to assess the state of SHP2 expression in breast cancer cells and in infiltrating ductal carcinoma (IDC) of breast. The possible role of SHP2 in breast cancer cell transformation was determined by dominant-negative expression and anchorage-independent growth assays. All of the breast cancer cell lines tested and 72% of IDC breast tumours analysed had increased amounts of the SHP2 protein. In support of its positive role, dominant-negative SHP2 blocked anchorage-independent growth of breast cancer cells. Furthermore, overexpression of SHP2 seemed to have a positive relationship to HER2 overexpression, nuclear accumulation of hormone receptors, higher tumour grade and lymph node metastasis, but not to age of breast cancer patients.

Conclusion:  SHP2 is a widely overexpressed signalling protein in IDC breast tumours. Given SHP2’s positive role in cell growth, transformation and stem cell survival, the positive relationship of its overexpression to lymph node metastasis, nuclear accumulation of hormone receptors and higher tumour grade suggests that SHP2 promotes breast oncogenesis.

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