Activation of Src by protein tyrosine phosphatase 1B Is required for ErbB2 transformation of human breast epithelial cells.
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.
Arias-Romero
Luis E
LE
Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.
Saha
Sayanti
S
Villamar-Cruz
Olga
O
Yip
Shu-Chin
SC
Ethier
Stephen P
SP
Zhang
Zhong-Yin
ZY
Chernoff
Jonathan
J
D002455:Cell Division / Q000235:genetics / Q000502:physiology; D002470:Cell Survival / Q000235:genetics / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D018734:Genes, erbB-2 / Q000502:physiology*; D006801:Humans; D042361:Mammary Glands, Human / Q000378:metabolism / Q000473:pathology* / Q000502:physiology; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics; D014162:Transfection
D016392:Proto-Oncogene Proteins pp60(c-src); D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1