Gene expression deregulation by KRAS G12D and G12V in a BRAF V600E context

Massimiliano Monticone, Emanuela Biollo, Massimo Maffei, Alessandra Donadini, Francesco Romeo, Clelia Tiziana Storlazzi, Walter Giaretti, Patrizio Castagnola

Research output: Contribution to journalArticle

Abstract

Background: KRAS and BRAF mutations appear of relevance in the genesis and progression of several solid tumor types but the co-occurrence and interaction of these mutations have not yet been fully elucidated. Using a microsatellite stable (MSS) colorectal cancer (CRC) cell line (Colo741) having mutated BRAF and KRASWT, we also aimed to investigate the KRAS-BRAF interaction. Gene expression profiles for control KRASWT, KRASG12V and KRASG12D transfected cells were obtained after cell clone selection and RT-PCR screening. Extensive qPCR was performed to confirm microarray data. Results: We found that the KRASG12V state deregulated several genes associated to cell cycle, apoptosis and nitrogen metabolism. These findings indicated a reduced survival and proliferation with respect to the KRASWT state. The KRASG12D state was, instead, characterized by several other distinct functional changes as for example those related to chromatin organization and cell-cell adhesion without affecting apoptosis related genes. Conclusion: These data predict that the G12D mutation may be more likely selected in a BRAF mutated context. At the same time, the presence of the KRASG12V mutation in the cells escaping apoptosis and inducing angiogenesis via IL8 may confer a more aggressive phenotype. The present results get along with the observations that CRCs with G12V are associated with a worse prognosis with respect to the WT and G12D states and may help identifying novel CRC pathways and biomarkers of clinical relevance.

Original languageEnglish
Article number92
JournalMolecular Cancer
Volume7
DOIs
Publication statusPublished - Dec 16 2008

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Medicine
  • Oncology

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    Monticone, M., Biollo, E., Maffei, M., Donadini, A., Romeo, F., Storlazzi, C. T., Giaretti, W., & Castagnola, P. (2008). Gene expression deregulation by KRAS G12D and G12V in a BRAF V600E context. Molecular Cancer, 7, [92]. https://doi.org/10.1186/1476-4598-7-92