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Genes Dev. 2007 Feb 15;21(4):379-84. Epub 2007 Feb 13.

A new mouse model to explore the initiation, progression, and therapy of BRAFV600E-induced lung tumors.

Author information

1
Cancer Research Institute, Department of Cellular and Molecular Pharmacology, University of California, San Francisco Comprehensive Cancer Center, California 94143, USA.

Abstract

Mutationally activated BRAF(V600E) (BRAF(VE)) is detected in approximately 6% of human malignancies and promotes sustained MEK1/2-ERK1/2 pathway activation. We have designed BRaf(CA) mice to express normal BRaf prior to Cre-mediated recombination after which BRaf(VE) is expressed at physiological levels. BRaf(CA) mice infected with an Adenovirus expressing Cre recombinase developed benign lung tumors that only rarely progressed to adenocarcinoma. Moreover, BRaf(VE)-induced lung tumors were prevented by pharmacological inhibition of MEK1/2. BRaf(VE) expression initially induced proliferation that was followed by growth arrest bearing certain hallmarks of senescence. Consistent with Ink4a/Arf and TP53 tumor suppressor function, BRaf(VE) expression combined with mutation of either locus led to cancer progression.

PMID:
17299132
PMCID:
PMC1804325
DOI:
10.1101/gad.1516407
[Indexed for MEDLINE]
Free PMC Article

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