Gene expression deregulation by <it>KRAS </it>G12D and G12V in a <it>BRAF </it>V600E context

• Main Authors: Romeo Francesco, Donadini Alessandra, Maffei Massimo, Biollo Emanuela, Monticone Massimiliano, Storlazzi Clelia, Giaretti Walter, Castagnola Patrizio
• Format: Article
• Language: English
• Published: BMC 2008-12-01
• Series: Molecular Cancer
• Online Access: http://www.molecular-cancer.com/content/7/1/92

<p>Abstract</p> <p>Background</p> <p><it>KRAS </it>and <it>BRAF </it>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 <it>BRAF </it>and <it>KRAS</it>^<it>WT</it>, we also aimed to investigate the <it>KRAS-BRAF </it>interaction. Gene expression profiles for control <it>KRAS</it>^<it>WT</it>, <it>KRAS</it>^{<it>G</it>12<it>V </it>}and <it>KRAS</it>^{<it>G</it>12<it>D </it>}transfected cells were obtained after cell clone selection and RT-PCR screening. Extensive qPCR was performed to confirm microarray data.</p> <p>Results</p> <p>We found that the <it>KRAS</it>^{<it>G</it>12<it>V </it>}state deregulated several genes associated to cell cycle, apoptosis and nitrogen metabolism. These findings indicated a reduced survival and proliferation with respect to the <it>KRAS</it>^{<it>WT </it>}state. The <it>KRAS</it>^{<it>G</it>12<it>D </it>}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.</p> <p>Conclusion</p> <p>These data predict that the G12D mutation may be more likely selected in a <it>BRAF </it>mutated context. At the same time, the presence of the <it>KRAS</it>^{<it>G</it>12<it>V </it>}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.</p>