Lkb1 loss promotes tumor progression of BRAF(V600E)-induced lung adenomas.
PLoS One
; 8(6): e66933, 2013.
Article
in En
| MEDLINE
| ID: mdl-23825589
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Adenoma
/
Protein Serine-Threonine Kinases
/
Gene Deletion
/
Disease Progression
/
Proto-Oncogene Proteins B-raf
/
Lung Neoplasms
/
Mutation
Type of study:
Risk_factors_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
PLoS One
Journal subject:
CIENCIA
/
MEDICINA
Year:
2013
Type:
Article
Affiliation country:
Spain