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.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Cell Division / genetics
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Cell Division / physiology
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Cell Survival / genetics
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Cell Survival / physiology
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Cell Transformation, Neoplastic / genetics
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Cell Transformation, Neoplastic / metabolism*
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Cells, Cultured
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Enzyme Activation
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Epithelial Cells / metabolism
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Epithelial Cells / pathology
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Epithelial Cells / physiology
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Genes, erbB-2 / physiology*
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Humans
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Mammary Glands, Human / metabolism
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Mammary Glands, Human / pathology*
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Mammary Glands, Human / physiology
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Protein Tyrosine Phosphatase, Non-Receptor Type 1 / genetics
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Protein Tyrosine Phosphatase, Non-Receptor Type 1 / metabolism
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Protein Tyrosine Phosphatase, Non-Receptor Type 1 / physiology*
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Proto-Oncogene Proteins pp60(c-src) / metabolism*
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Proto-Oncogene Proteins pp60(c-src) / physiology
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Signal Transduction / genetics
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Transfection
Substances
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Proto-Oncogene Proteins pp60(c-src)
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Protein Tyrosine Phosphatase, Non-Receptor Type 1