Xie Y, Hung M C
Department of Tumor Biology and Breast Cancer Basic Research Program, The University of Texas M.D. Anderson Cancer Center, Houston, 77030, USA.
Biochem Biophys Res Commun. 1996 Apr 5;221(1):140-5. doi: 10.1006/bbrc.1996.0559.
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.
HER2/neu原癌基因编码一种分子量为185 kDa的跨膜受体酪氨酸激酶（称为p185），其在结构和功能上与表皮生长因子受体同源。Shc蛋白是受体酪氨酸激酶重要的下游信号转导分子。我们在此报告一项新发现：在p185过表达的乳腺癌细胞中，p66Shc缺失或几乎缺失。p185过表达与p66Shc表达的这种负相关可能是乳腺癌细胞特有的，因为在p185过表达的人卵巢癌、肺癌或口腔癌细胞，或小鼠成纤维细胞中未观察到这种现象。相反，在p185过表达和p185基础水平的乳腺癌细胞系中，p52Shc和p46Shc亚型的表达水平相似。此外，在p185酪氨酸激酶被激活的乳腺癌细胞中检测到p52Shc和p46Shc的酪氨酸磷酸化以及随后Shc/Grb2复合物的形成，这表明p66Shc不是介导乳腺癌细胞中HER-2/neu信号通路所必需的。
