Chen Y Q, Zhou Y Q, Angeloni D, Kurtz A L, Qiang X Z, Wang M H
Department of Medicine, University of Colorado School of Medicine and Denver Health Medical Center, Denver, Colorado 80204, USA.
Exp Cell Res. 2000 Nov 25;261(1):229-38. doi: 10.1006/excr.2000.5012.
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 (RONDelta160) was identified from HT-29 cells. The cDNA encoding RONDelta160 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 RON 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.
RON是一种属于MET原癌基因家族的受体酪氨酸激酶。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情况。蛋白质印迹法显示，在正常和SV - 40转化的结肠上皮细胞中几乎检测不到RON，但在包括Colo201、HT - 29、HCT116和SW837在内的几种结肠癌细胞系中高表达且组成性激活。此外，从HT - 29细胞中鉴定出一种分子量为160 kDa的新型RON变体（RONDelta160）。编码RONDelta160的cDNA在RONβ链的胞外结构域有109个氨基酸的框内缺失，这是由RON mRNA中两个外显子的剪接缺失导致的。在筛选的五个癌细胞系中，RON基因的激酶结构域未发现突变。通过在结肠上皮细胞中表达RON，我们发现RON激活增加细胞的运动侵袭活性并保护细胞免于凋亡死亡。这些数据表明，在结肠癌细胞系中RON的表达和激活失调。通过RON的异常激活，该受体及其变体可能在体内调节某些结肠癌细胞的运动侵袭表型。
