This Article Full Text Full Text (PDF) Supplementary Data All Versions of this Article: 0008-5472.CAN-08-4001v1 69/11/4582    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Arias-Romero, L. E. Articles by Chernoff, J. PubMed PubMed Citation Articles by Arias-Romero, L. E. Articles by Chernoff, J.

Activation of Src by Protein Tyrosine Phosphatase 1B Is Required for ErbB2 Transformation of Human Breast Epithelial Cells

¹ Fox Chase Cancer Center, Philadelphia, Pennsylvania; ² Karmanos Cancer Institute, Department of Pathology, Wayne State University School of Medicine, Detroit, Michigan; and ³ Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana

Requests for reprints: Jonathan Chernoff, Fox Chase Cancer Center, Philadelphia, PA. Phone: 215-728-5319; Fax: 215-28-3616; E-mail: J_Chernoff{at}fccc.edu.

Key Words: transformation • protein tyrosine phosphatase • ErbB2 • signal transduction • breast cancer • oncogene

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. [Cancer Res 2009;69(11):4582–8]