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.
Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.
Luis E
LE
Arias-Romero
Sayanti
S
Saha
Olga
O
Villamar-Cruz
Shu-Chin
SC
Yip
Stephen P
SP
Ethier
Zhong-Yin
ZY
Zhang
Jonathan
J
Chernoff
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