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C-Raf, but not B-Raf, is essential for development of K-Ras oncogene-driven non-small cell lung carcinoma.

ABSTRACT: We have investigated the role of individual members of the Raf/Mek/Erk cascade in the onset of K-Ras oncogene-driven non-small cell lung carcinoma (NSCLC). Ablation of Erk1 or Erk2 in K-Ras oncogene-expressing lung cells had no significant effect due to compensatory activities. Yet, elimination of both Erk kinases completely blocked tumor development. Similar results were obtained with Mek kinases. Ablation of B-Raf had no significant effect on tumor development. However, c-Raf expression was absolutely essential for the onset of NSCLC. Interestingly, concomitant elimination of c-Raf and B-Raf in adult mice had no deleterious consequences for normal homeostasis. These results indicate that c-Raf plays a unique role in mediating K-Ras signaling and makes it a suitable target for therapeutic intervention.

SUBMITTER: Blasco RB

PROVIDER: S-EPMC4854330 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature

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c-Raf, but not B-Raf, is essential for development of K-Ras oncogene-driven non-small cell lung carcinoma.

Blasco Rafael B RB Francoz Sarah S Santamaría David D Cañamero Marta M Dubus Pierre P Charron Jean J Baccarini Manuela M Barbacid Mariano M

Cancer cell 20110421 5

We have investigated the role of individual members of the Raf/Mek/Erk cascade in the onset of K-Ras oncogene-driven non-small cell lung carcinoma (NSCLC). Ablation of Erk1 or Erk2 in K-Ras oncogene-expressing lung cells had no significant effect due to compensatory activities. Yet, elimination of both Erk kinases completely blocked tumor development. Similar results were obtained with Mek kinases. Ablation of B-Raf had no significant effect on tumor development. However, c-Raf expression was ab ...[more]

PMID: 21514245

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