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Rare codons capacitate Kras-driven de novo tumorigenesis.

Publication ,  Journal Article
Pershing, NLK; Lampson, BL; Belsky, JA; Kaltenbrun, E; MacAlpine, DM; Counter, CM
Published in: J Clin Invest
January 2015

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.

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Published In

J Clin Invest

DOI

EISSN

1558-8238

Publication Date

January 2015

Volume

125

Issue

1

Start / End Page

222 / 233

Location

United States

Related Subject Headings

  • Urethane
  • Tumor Burden
  • Proto-Oncogene Proteins p21(ras)
  • Mice, Transgenic
  • Mice, Inbred C57BL
  • Mice, 129 Strain
  • Male
  • Lung Neoplasms
  • Immunology
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Pershing, N. L. K., Lampson, B. L., Belsky, J. A., Kaltenbrun, E., MacAlpine, D. M., & Counter, C. M. (2015). Rare codons capacitate Kras-driven de novo tumorigenesis. J Clin Invest, 125(1), 222–233. https://doi.org/10.1172/JCI77627
Pershing, Nicole L. K., Benjamin L. Lampson, Jason A. Belsky, Erin Kaltenbrun, David M. MacAlpine, and Christopher M. Counter. “Rare codons capacitate Kras-driven de novo tumorigenesis.J Clin Invest 125, no. 1 (January 2015): 222–33. https://doi.org/10.1172/JCI77627.
Pershing NLK, Lampson BL, Belsky JA, Kaltenbrun E, MacAlpine DM, Counter CM. Rare codons capacitate Kras-driven de novo tumorigenesis. J Clin Invest. 2015 Jan;125(1):222–33.
Pershing, Nicole L. K., et al. “Rare codons capacitate Kras-driven de novo tumorigenesis.J Clin Invest, vol. 125, no. 1, Jan. 2015, pp. 222–33. Pubmed, doi:10.1172/JCI77627.
Pershing NLK, Lampson BL, Belsky JA, Kaltenbrun E, MacAlpine DM, Counter CM. Rare codons capacitate Kras-driven de novo tumorigenesis. J Clin Invest. 2015 Jan;125(1):222–233.

Published In

J Clin Invest

DOI

EISSN

1558-8238

Publication Date

January 2015

Volume

125

Issue

1

Start / End Page

222 / 233

Location

United States

Related Subject Headings

  • Urethane
  • Tumor Burden
  • Proto-Oncogene Proteins p21(ras)
  • Mice, Transgenic
  • Mice, Inbred C57BL
  • Mice, 129 Strain
  • Male
  • Lung Neoplasms
  • Immunology
  • Humans