Differences in in vitro invasive capacity induced by differences in Ki-Ras protein mutations

被引:30
作者
Al-Mulla, F
MacKenzie, EM
机构
[1] Kuwait Univ, Fac Med, Dept Pathol, Mol Pathol Lab, Safat 13110, Kuwait
[2] Beatson Inst Canc Res, CRC, Beatson Labs, Glasgow G61 1BD, Lanark, Scotland
关键词
Ras; Ras mutants; in vitro invasion; signal transduction; aggression;
D O I
10.1002/path.995
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The p21 proteins encoded by N-, Ki-, and H-ras are small guanine nucleotide-binding proteins that act as switches in several signal transduction pathways. Recently, evidence has been accumulating to suggest that valine-12 mutation in the Ki-Ras protein is associated with lung and colorectal tumours that are more aggressive than those carrying aspartate-12 mutation. The purpose of this study was to determine whether cells transfected with different Ki-ras codon-12 mutants have different biological behaviours in vitro that could reflect the differences in behaviour in vivo. For that reason, Rat-1 fibroblasts transfected with the valine-12 or aspartate-12 mutant or the wild-type Ki-ras gene were assessed in terms of in vitro invasion, transformation, and VEGF production. Both mutants demonstrated equal abilities to transform Rat-1 cells and induce VEGF production, while cells transfected with wild-type Ki-Ras failed to do so. Most significantly, the valine-12 mutants demonstrated a greater ability to invade Matrigel than cells expressing the aspartate-12 mutant or wild-type Ki-Ras proteins. This study complements previous experimental data that specific Ras mutations differ in their effects in vivo and shows, for the first time, a significant difference in Matrigel invasion in vitro. The precise mechanisms behind these biological differences in vivo and in vitro should now be investigated. Copyright (C) 2001 John Wiley & Sons, Ltd.
引用
收藏
页码:549 / 556
页数:8
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