A novel activating mutation of the K-ras gene in human primary colon adenocarcinoma.
We identified a novel type of point mutation at the 22nd codon of the K-ras gene in a primary colon cancer. The mutation was C to A transversion substituting lysine (AAG) for normal glutamine (CAG) codon. Biological activity of this mutant K-ras gene was tested by expression of full-length cDNA clones in NIH3T3 cells. Most of the K-ras Lys22-transfected cells exhibited an increased saturation density, a lower serum requirement, and transformed morphology reminiscent to the typical K-ras Val12 transformants. However, the tumorigenicity of K-ras Lys22 transformants in nude mice was significantly less potent than that of K-ras Val12 transformants; only a high copy number transformant produced tumors. Even though the activation is incomplete, the finding that the majority of tumor cells in the specimen carried the K-ras Lys22 mutation suggests that this mutation might be advantageous for growth of tumor cells in vivo.
Tsukuda
K
K
Department of Molecular Genetics, Second Department of Surgery, Okayama University Medical School, Shikata-cho 2-5-1, Okayama, 700-8558, Japan.
Tanino
M
M
Soga
H
H
Shimizu
N
N
Shimizu
K
K
D016475:3T3 Cells; D000225:Adenine; D000230:Adenocarcinoma / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D003110:Colonic Neoplasms / Q000235:genetics*; D003596:Cytosine; D011905:Genes, ras; D006801:Humans; D008239:Lysine; D051379:Mice; D008819:Mice, Nude; D017354:Point Mutation; D011994:Recombinant Proteins / Q000096:biosynthesis; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
D011994:Recombinant Proteins; D003596:Cytosine; D000225:Adenine; D008239:Lysine