Activation of c-Met (hepatocyte growth factor receptor) in human gastric cancer tissue
Activation of c-Met (hepatocyte growth factor receptor) in human gastric cancer tissue
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DOI：
10.1111/j.1349-7006.2004.tb02185.x
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发表时间：
2004-10-01
期刊：
影响因子：
5.7
通讯作者：
Miyazawa, K
中科院分区：
文献类型：
--
作者：
Inoue, T;Kataoka, H;Miyazawa, K
c-Met是肝细胞生长因子（HGF）的高亲和力受体，在胚胎发育以及组织修复过程中起着至关重要的作用。c-Met在多种肿瘤组织中，尤其是胃癌组织中的过度表达和扩增是常见的。然而，尚不清楚过表达是否导致c-Met受体的激活。为了解决这一点，我们制备了特异性识别在Y1235（c-Met的主要磷酸化位点）磷酸化的c-Met的抗体（抗磷酸化-Met）。正常胃组织和癌组织抗总甲硫氨酸染色阳性，而只有癌组织抗磷酸化甲硫氨酸染色强阳性;基底层附近的细胞呈中度阳性，正常组织中的增殖区仅呈弱阳性。在本研究中检查的7名患者的癌组织中，6名患者的癌组织对磷酸化-Met染色呈强阳性。这些结果表明，c-Met在胃癌组织中实际上被激活，并且可能触发增殖/抗凋亡信号。
c-Met is a high-affinity receptor for hepatocyte growth factor (HGF) and plays a crucial role in embryonic development, as well as in the process of tissue repair. Overexpression and amplification of c-Met are often observed in various cancer tissues, especially in gastric carcinoma. It has, however, been unclear whether the overexpression leads to activation of the c-Met receptor. To address this point, we prepared an antibody (anti-phospho-Met) which specifically recognizes c-Met that is phosphorylated at Y1235, a major phosphorylation site of c-Met. Normal as well as cancerous gastric tissue was positive for anti-total-Met staining, whereas only cancerous tissue was strongly positive for antiphospho-Met staining; cells near the basal layer were moderately positive, and the proliferative zone in normal tissue was only weakly positive. Among cancerous tissues from seven patients examined in the present study, those from six patients were strongly positive for phospho-Met staining. These results indicate that c-Met is actually activated in gastric carcinoma tissue, and may trigger proliferation /anti-apoptotic signals.