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Molecular Cancer
Published in: Molecular Cancer 1/2008

Open Access 01-12-2008 | Research

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

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

Published in: Molecular Cancer | Issue 1/2008

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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 KRAS WT , we also aimed to investigate the KRAS-BRAF interaction. Gene expression profiles for control KRAS WT , KRASG 12Vand KRASG 12Dtransfected cells were obtained after cell clone selection and RT-PCR screening. Extensive qPCR was performed to confirm microarray data.

Results

We found that the KRASG 12Vstate deregulated several genes associated to cell cycle, apoptosis and nitrogen metabolism. These findings indicated a reduced survival and proliferation with respect to the KRAS WT state. The KRASG 12Dstate 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 KRASG 12Vmutation 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.
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Metadata
Title
Gene expression deregulation by KRAS G12D and G12V in a BRAF V600E context
Authors
Massimiliano Monticone
Emanuela Biollo
Massimo Maffei
Alessandra Donadini
Francesco Romeo
Clelia Tiziana Storlazzi
Walter Giaretti
Patrizio Castagnola
Publication date
01-12-2008
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2008
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/1476-4598-7-92

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