Lkb1 Loss Promotes Tumor Progression of BRAF.sup.V600E-Induced Lung Adenomas

Aberrant activation of MAP kinase signaling pathway and loss of tumor suppressor LKB1 have been implicated in lung cancer development and progression. Although oncogenic KRAS mutations are frequent, BRAF mutations (BRAF.sup.V600E) are found in 3% of human non-small cell lung cancers. Contrary to KRA...

Full description

Saved in:
Bibliographic Details
Published in:PloS one 2013-06, Vol.8 (6), p.e66933
Main Authors: González-Sánchez, Elena, Martín-Caballero, Juan, Flores, Juana María, Hernández-Losa, Javier, Cortés, Javier, Mares, Roso, Barbacid, Mariano, Recio, Juan A
Format: Article
Language:English
Subjects:
Development and progression
Gene mutation
Genetic aspects
Non-small cell lung cancer
Tumors
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Aberrant activation of MAP kinase signaling pathway and loss of tumor suppressor LKB1 have been implicated in lung cancer development and progression. Although oncogenic KRAS mutations are frequent, BRAF mutations (BRAF.sup.V600E) are found in 3% of human non-small cell lung cancers. Contrary to KRAS mutant tumors, BRAF.sup.V600E -induced tumors are benign adenomas that fail to progess. Interestingly, loss of tumor supressor LKB1 coexists with KRAS oncogenic mutations and synergizes in tumor formation and progression, however, its cooperation with BRAF.sup.V600E oncogene is unknown. Our results describe a lung cell population in neonates mice where expression of BRAF.sup.V600E leads to lung adenoma development. Importantly, expression of BRAF.sup.V600E concomitant with the loss of only a single-copy of Lkb1, overcomes senencence-like features of BRAF.sup.V600E -mutant adenomas leading malignization to carcinomas. These results posit LKB1 haploinsufficiency as a risk factor for tumor progression of BRAF.sup.V600E mutated lung adenomas in human cancer patients.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0066933