p66Shc isoform down-regulated and not required for HER-2/neu signaling pathway in human breast cancer cell lines with HER-2/neu overexpression.
The HER2/neu protooncogene encodes a transmembrane receptor tyrosine kinase of Mr185 kDa (called p185) which is structurally and functionally homologous to the epidermal growth factor receptor. Shc proteins are important downstream signal transducers of receptor tyrosine kinases. We reported here a novel finding that p66Sch was absent or nearly absent in p185-overexpressing breast cancer cells. This inverse correlation of p185 overexpression and p66Shc expression is probably specific to breast cancer cells because this phenomenon was not observed in p185-overexpressing human ovarian, lung, or oral cancer cells, or mouse fibroblast cells. In contrast, the p52Shc and p46Shc isoforms were expressed at similar levels in both p185-overexpressing and p185 basal level breast cancer cell lines. Furthermore, tyrosine phosphorylation of p52Shc and p46Shc and subsequent formation of Shc/Grb2 complex were detected in breast cancer cells in which the p185 tyrosine kinase is activated, indicating that p66Shc is not required for mediating the HER-2/neu signaling pathway in breast cancer cells.
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Department of Tumor Biology and Breast Cancer Basic Research Program, The University of Texas M.D. Anderson Cancer Center, Houston, 77030, USA.
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D016475:3T3 Cells; D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D006801:Humans; D051379:Mice; D011506:Proteins / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D055765:Shc Signaling Adaptor Proteins; D015398:Signal Transduction; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D014407:Tumor Cells, Cultured
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D011506:Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D055765:Shc Signaling Adaptor Proteins; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; C528024:SHC1 protein, human; C528034:Shc1 protein, mouse