Interplay between oncogenic K-Ras and wild-type H-Ras in Caco2 cell transformation

Georgia Ikonomou, Vassiliki Kostourou, Senji Shirasawa, Takehiko Sasazuki, Martina Samiotaki, George Panayotou

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6 Citations (Scopus)

Abstract

Mutation of RAS genes is one of the most common oncogenic alterations in cancer and acquisition of activating RAS mutations has been demonstrated to cause progression of colorectal adenoma to cancer. The aim of this study was to identify changes in the proteome of the intermediate-stage colorectal cancer cell line Caco2, induced by ectopic expression of two distinct RAS proteins, KRASV12 and HRASV12, in their mutated, constitutively active form. Using 2D-gel electrophoresis, followed by LC-MS/MS we identified almost 200 differentially expressed proteins in pair-wise comparisons of Caco2 vs Caco2-KRASV12 and Caco2 vs Caco2-HRASV12. Although many of the affected proteins were unique for each pair, there were also substantial similarities. Interestingly, transformation by the mutant KRASV12 gene resulted in elevated expression levels and activity of endogenous H-ras protein. Silencing the latter with a specific RNAi reversed several proteomic changes observed in KRASV12-transformed cells, suggesting that oncogenic K-ras partly exerts its effects through endogenous H-ras activation. Alterations in the expression of cytoskeletal and cell adhesion proteins, caused by HRAS siRNA treatment, correlated with a reduction in the invasive properties of Caco2-KRASV12 cells. Our data suggest a novel interplay between K-ras and H-ras, with possible implications for colorectal carcinogenesis.

Original languageEnglish
Pages (from-to)5356-5369
Number of pages14
JournalJournal of Proteomics
Volume75
Issue number17
DOIs
Publication statusPublished - Sep 18 2012
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry

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    Ikonomou, G., Kostourou, V., Shirasawa, S., Sasazuki, T., Samiotaki, M., & Panayotou, G. (2012). Interplay between oncogenic K-Ras and wild-type H-Ras in Caco2 cell transformation. Journal of Proteomics, 75(17), 5356-5369. https://doi.org/10.1016/j.jprot.2012.06.038