Lkb1 Loss Promotes Tumor Progression of BRAF V600E -Induced Lung Adenomas
González-Sánchez, Elena (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Martín-Caballero, Juan (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Flores, Juana María (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Hernandez-Losa, Javier (Hospital Universitari Vall d'Hebron)
Cortés, Javier (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Marés, Roso (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Barbacid, Mariano (Centro Nacional de Investigaciones Oncológicas)
Recio Conde, Juan Ángel (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Universitat Autònoma de Barcelona

Date:	2013
Abstract:	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 V600E) are found in 3% of human non-small cell lung cancers. Contrary to KRAS mutant tumors, BRAF 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 V600E oncogene is unknown. Our results describe a lung cell population in neonates mice where expression of BRAF V600E leads to lung adenoma development. Importantly, expression of BRAF V600E concomitant with the loss of only a single-copy of Lkb1, overcomes senencence-like features of BRAF V600E -mutant adenomas leading malignization to carcinomas. These results posit LKB1 haploinsufficiency as a risk factor for tumor progression of BRAF V600E mutated lung adenomas in human cancer patients.
Grants:	Ministerio de Ciencia e Innovación PI080653 Ministerio de Ciencia e Innovación PI1100384
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	PloS one, Vol. 8 (june 2013) , ISSN 1932-6203

DOI: 10.1371/journal.pone.0066933
PMID: 23825589

8 p, 3.1 MB

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