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Cancer Res. 2009 Jun 1;69(11):4582-8. doi: 10.1158/0008-5472.CAN-08-4001. Epub 2009 May 12.

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

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  • 1Fox 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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