Activation of ErB3-PI3-kinase pathway is correlated with malignant phenotypes of adenocarcinomas
Activation of ErB3-PI3-kinase pathway is correlated with malignant phenotypes of adenocarcinomas
复制标题
DOI：
10.1038/sj.onc.1206256
复制
发表时间：
2003-03-06
期刊：
影响因子：
8
通讯作者：
Fukui, Y
中科院分区：
文献类型：
--
作者：
Kobayashi, M;Iwamatsu, A;Fukui, Y
印戒细胞癌是恶性去分化癌，常见于胃。我们以前证明，一个200 kDa的蛋白质往往是组成性磷酸化酪氨酸和结合到磷脂酰肌醇3-激酶（PI 3-激酶）印戒细胞癌细胞。在这项研究中，我们纯化的200 kDa的蛋白质提取物的NUGC-4细胞，印戒细胞癌的细胞系，并确定为ErbB 3。ErbB 3在各种胃癌细胞系中被发现在去分化腺癌细胞系中被选择性地磷酸化。ErbB 2和ErbB 3组成型活性嵌合受体在高度分化的腺癌细胞系HCC 2998中的表达揭示了ErbB 3磷酸化引发的信号传导对于去分化表型如细胞-细胞相互作用的丧失和恶性肿瘤标志物MUC 1/DF 3抗原的高表达是重要的。综上所述，ErbB 3通路的激活可能有助于去分化癌的发展。
Signet-ring cell carcinomas are malignant dedifferentiated carcinomas, which are frequently found in the stomach. We previously demonstrated that a 200 kDa protein is often constitutively phosphorylated on tyrosine and bound to phosphatidylinositol 3-kinase (PI3-kinase) in signet-ring cell carcinoma cells. In this study, we purified the 200 kDa protein from an extract of NUGC-4 cells, a cell line of signet-ring cell carcinoma, and identified it as ErbB3. ErbB3 was found to be phosphorylated selectively in dedifferentiated adenocarcinoma cell lines among various gastric cancer cell lines. Expression of a constitutively active chimeric receptor consisting of ErbB2 and ErbB3 in HCC2998 cells, a highly differentiated adenocarcinoma cell line, revealed that the signaling triggered by phosphorylation of ErbB3 was important for dedifferentiated phenotypes such as loss of cell-cell interaction and high expression of MUC1/DF3 antigen, a marker of the malignant tumors. Taken together, activation of ErbB3 pathway may contribute to the development of dedifferentiated carcinomas.