Kruppel-like factor 5 is not required for K-RasG12D lung tumorigenesis, but represses ABCG2 expression and is associated with better disease-specific survival.
Am J Pathol
; 177(3): 1503-13, 2010 Sep.
Article
en En
| MEDLINE
| ID: mdl-20639455
ABSTRACT
K-RAS mutations are found in approximately 30% of lung cancers. The transcription factor Krüppel-like Factor 5 (KLF5) has been shown to mediate cellular transformation signaling events downstream of oncogenic RAS in other cancers, but a role for KLF5 in lung tumorigenesis has not been defined. We show here that knockdown of KLF5 expression significantly decreased anchorage-independent growth, but did not affect proliferation of human lung adenocarcinoma cells. Moreover, Klf5 is not required for lung tumor formation in an inducible oncogenic K-Ras(G12D) mouse model of lung tumorigenesis, and non-small cell lung cancer patients expressing high levels of KLF5 (21/258) have a significantly better disease-specific survival than those with intermediate to no KLF5 expression. Further, KLF5 knockdown in K-RAS-mutant human lung cancer cells resulted in a fivefold increase in ATP-binding cassette, subfamily G (WHITE), member 2 (ABCG2), an anthracycline drug transporter, which lead to significantly increased resistance to doxorubicin treatment, a chemotherapeutic agent clinically used to treat lung cancer. In summary, while KLF5 is not required for oncogenic mutant K-Ras-induced lung tumorigenesis, KLF5 regulation of ABCG2 expression may be important for chemotherapeutic resistance and patient survival.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Proteínas Proto-Oncogénicas
/
Carcinoma de Pulmón de Células no Pequeñas
/
Proteínas ras
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Transportadoras de Casetes de Unión a ATP
/
Factores de Transcripción de Tipo Kruppel
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Neoplasias Pulmonares
/
Proteínas de Neoplasias
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Am J Pathol
Año:
2010
Tipo del documento:
Article
País de afiliación:
Estados Unidos