Takeshima E, Hamaguchi M, Watanabe T, Akiyama S, Kataoka M, Ohnishi Y, Xiao H Y, Nagai Y, Takagi H
Department of Surgery II, Nagoya University School of Medicine.
Jpn J Cancer Res. 1991 Dec;82(12):1428-35. doi: 10.1111/j.1349-7006.1991.tb01816.x.
Phosphotyrosine-containing proteins in various human cancer cell lines were studied by immunoblotting with anti-phosphotyrosine antibody. Of 29 cell lines derived from oral epidermoid cancer, esophageal cancer, gastric cancer, colon cancer, pancreatic cancer, hepatocellular carcinoma and malignant melanoma, 3 of the 6 gastric cancer cells showed aberrant elevation of tyrosine-specific phosphorylation. On the other hand, both esophageal cancer cells and colon cancer cells, which were reported to have amplified epidermal growth factor receptor and activated p60v-src kinase, respectively, showed no apparent elevation of tyrosine-specific phosphorylation, and their profiles of phosphorylation were similar to that of normal human fibroblasts. Two gastric cancer cells, NUGC-4 and MKN-45, showed similar profiles of phosphorylation but their responses to growth factors differed from each other. Tyrosine phosphorylation in NUGC-4 was strongly activated by treatment with epidermal growth factor and quickly reduced by the acid treatment which is effective in removing growth factors from cellular surface receptors. On the contrary, phosphorylation in MKN-45 did not respond to either growth factor or acid treatment. These results suggest that NUGC-4 and MKN-45 have tyrosine kinases which are activated by different mechanisms but share similar substrates.
通过使用抗磷酸酪氨酸抗体进行免疫印迹，对多种人类癌细胞系中含磷酸酪氨酸的蛋白质进行了研究。在源自口腔表皮样癌、食管癌、胃癌、结肠癌、胰腺癌、肝细胞癌和恶性黑色素瘤的29个细胞系中，6个胃癌细胞系中有3个显示酪氨酸特异性磷酸化异常升高。另一方面，据报道分别具有扩增的表皮生长因子受体和活化的p60v-src激酶的食管癌细胞和结肠癌细胞，未显示酪氨酸特异性磷酸化有明显升高，并且它们的磷酸化谱与正常人成纤维细胞相似。两种胃癌细胞NUGC-4和MKN-45显示出相似的磷酸化谱，但它们对生长因子的反应彼此不同。用表皮生长因子处理可强烈激活NUGC-4中的酪氨酸磷酸化，而用酸处理可迅速降低酪氨酸磷酸化，酸处理可有效从细胞表面受体去除生长因子。相反，MKN-45中的磷酸化对生长因子或酸处理均无反应。这些结果表明，NUGC-4和MKN-45具有通过不同机制激活但共享相似底物的酪氨酸激酶。
