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    Cancer Res. 2009 Jun 1;69(11):4582-8. Epub 2009 May 12.

    Activation of Src by protein tyrosine phosphatase 1B Is required for ErbB2 transformation of human breast epithelial cells.

    Source

    Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.

    Abstract

    Protein tyrosine phosphatase (PTP) 1B plays a major role in inhibiting signaling from the insulin and leptin receptors. Recently, PTP1B was found to have an unexpected positive role in ErbB2 signaling in a mouse model of breast cancer, but the mechanism underlying this effect has been unclear. Using human breast epithelial cells grown in a three-dimensional matrix, we found that PTP1B, but not the closely related enzyme T-cell PTP, is required for ErbB2 transformation in vitro. Activation of ErbB2, but not ErbB1, increases PTP1B expression, and increased expression of PTP1B activates Src and induces a Src-dependent transformed phenotype. These findings identify a molecular mechanism by which PTP1B links an important oncogenic receptor tyrosine kinase to signaling pathways that promote aberrant cell division and survival in human breast epithelial cells.

    PMID:
    19435911
    [PubMed - indexed for MEDLINE]
    PMCID:
    PMC2692630
    Free PMC Article

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