Rare codons capacitate Kras-driven de novo tumorigenesis.

Published

Journal Article

The KRAS gene is commonly mutated in human cancers, rendering the encoded small GTPase constitutively active and oncogenic. This gene has the unusual feature of being enriched for rare codons, which limit protein expression. Here, to determine the effect of the rare codon bias of the KRAS gene on de novo tumorigenesis, we introduced synonymous mutations that converted rare codons into common codons in exon 3 of the Kras gene in mice. Compared with control animals, mice with at least 1 copy of this Kras(ex3op) allele had fewer tumors following carcinogen exposure, and this allele was mutated less often, with weaker oncogenic mutations in these tumors. This reduction in tumorigenesis was attributable to higher expression of the Kras(ex3op) allele, which induced growth arrest when oncogenic and exhibited tumor-suppressive activity when not mutated. Together, our data indicate that the inherent rare codon bias of KRAS plays an integral role in tumorigenesis.

Full Text

Duke Authors

Cited Authors

  • Pershing, NLK; Lampson, BL; Belsky, JA; Kaltenbrun, E; MacAlpine, DM; Counter, CM

Published Date

  • January 2015

Published In

Volume / Issue

  • 125 / 1

Start / End Page

  • 222 - 233

PubMed ID

  • 25437878

Pubmed Central ID

  • 25437878

Electronic International Standard Serial Number (EISSN)

  • 1558-8238

International Standard Serial Number (ISSN)

  • 0021-9738

Digital Object Identifier (DOI)

  • 10.1172/JCI77627

Language

  • eng