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Differences in in vitro invasive capacity induced by differences in Ki‐Ras protein mutations
Author(s) -
AlMulla Fahd,
MacKenzie Elaine M.
Publication year - 2001
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.995
Subject(s) - mutant , transfection , in vitro , biology , in vivo , microbiology and biotechnology , matrigel , mutation , wild type , signal transduction , gene , biochemistry , genetics
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 © 2001 John Wiley & Sons, Ltd.