A novel activating mutation of the K-ras gene in human primary colon adenocarcinoma

Kazunori Tsukuda, Motohiko Tanino, Hiroyuki Soga, Nobuyoshi Shimizu, Kenji Shimizu

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

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. (C) 2000 Academic Press.

Original languageEnglish
Pages (from-to)653-658
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume278
Issue number3
DOIs
Publication statusPublished - Nov 30 2000

Keywords

  • Colon cancer
  • K-ras
  • Mutation
  • Oncogene
  • Signaling
  • Transformation

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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