Overexpression and activation of the RON receptor tyrosine kinase in a panel of human colorectal carcinoma cell lines
Overexpression and activation of the RON receptor tyrosine kinase in a panel of human colorectal carcinoma cell lines
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DOI：
10.1006/excr.2000.5012
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发表时间：
2000-11-25
影响因子：
3.7
通讯作者：
Wang, MH
中科院分区：
文献类型：
--
作者：
Chen, YQ;Zhou, YQ;Wang, MH
RON是一种酪氨酸激酶受体，属于MET原癌基因家族。本研究的目的是确定RON在一组人结肠癌细胞系中的表达和激活。Western blotting显示，RON在正常和sv -40转化的结肠上皮细胞中几乎检测不到，但在包括col201、HT-29、HCT116和SW837在内的几种结肠癌细胞系中高度表达并组成性激活。此外，从HT-29细胞中鉴定出一种分子质量为160 kDa的RON变异（RON Delta 160）。编码RON Delta 160的cDNA在RON β链的胞外结构域有109个氨基酸的框内缺失，这是由RON mRNA的两个外显子剪接引起的。在筛选的5株癌细胞中，均未发现RON基因激酶结构域发生突变。通过在结肠上皮细胞中表达RON，我们发现BON激活增加了细胞的运动侵袭活性，并保护细胞免受凋亡死亡。这些数据表明结肠癌细胞系中RON的表达和激活是不受调控的。通过异常激活RON，该受体及其变异可能在体内调节某些结肠癌细胞的移动侵袭表型。(C) 2000年学术出版社。
RON is a receptor tyrosine kinase belonging to the MET proto-oncogene family. The purposes of this study are to determine the expression and activation of RON in a panel of human colon carcinoma cell lines. Western blotting showed that RON is barely detectable in normal and SV-40-transformed colon epithelial cells, but highly expressed and constitutively activated in several colon carcinoma cell lines including Colo201, HT-29, HCT116, and SW837. Moreover, a novel RON variant with a molecular mass of 160 kDa (RON Delta 160) was identified from HT-29 cells. The cDNA encoding RON Delta 160 has an in-frame deletion of 109 amino acids in the extracellular domain of the RON beta chain, which is caused by splicing out of two exons in the RON mRNA. No mutations were found in the kinase domain of the RON gene in five carcinoma cell lines screened. By expressing RON in colon epithelial cells, we found that BON activation increases cell motile-invasive activities and protects cells against apoptotic death. These data suggest that RON expression and activation are deregulated in colon carcinoma cell lines. By abnormal activation of RON, this receptor and its variant may regulate motile-invasive phenotypes of certain colon carcinoma cells in vivo. (C) 2000 Academic Press.