Diacylglycerol kinase n modualtes oncogenic properties of lung cancer cells
Clin. transl. oncol. (Print)
; 16(1): 29-35, ene. 2014. ilus
Artigo
em Inglês
| IBECS
| ID: ibc-127516
Biblioteca responsável:
ES1.1
Localização: BNCS
ABSTRACT
PURPOSE:
Lung cancer is a leading cause of cancer deaths and efforts are underway to identify novel therapies to treat these tumors. Diacylglycerol kinase η (DGKη), an enzyme that phosphorylates diacylglycerol to form phosphatidic acid, has been shown to modulate MAPK signaling downstream of EGFR, which is an oncogenic driver in some lung cancers. Since mutations in EGFR and K-Ras are common in lung cancer, we hypothesized that limiting the function of DGKη would attenuate oncogenic properties of lung cancer cells.METHODS:
We determined the expression levels of DGKη in a mouse models of mutant EGFR and K-Ras lung cancer and in human lung cancer cell lines with activating mutations in either EGFR or K-Ras. We also tested the effects of shRNA-mediated depletion of DGKη in lung cancer cells and tested if DGKη depletion augmented the effects of afatinib, a new generation EGFR inhibitor.RESULTS:
DGKη was expressed in malignant epithelium from mice with mutant EGFR or K-Ras lung cancer. It was also expressed in human lung cancer cell lines with EGFR or K-Ras mutations. Depleting DGKη in lung cancer cell lines, harboring mutant EGFR, reduced their growth on plastic and in soft agar and also augmented the effects of afatinib, an EGFR inhibitor. DGKη depletion also reduced growth of one of two lung cancer cell lines that harbored mutant K-Ras.CONCLUSIONS:
Our data indicate that DGKη is a potential therapeutic target in lung cancers, especially those harboring EGFR mutations. Our findings warrant further studies to examine the effects of limiting its function in vivo (AU)RESUMEN
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Bases de dados nacionais
/
Espanha
Contexto em Saúde:
ODS3 - Meta 3.4 Reduzir as mortes prematuras devido doenças não transmissíveis
Problema de saúde:
Outras Doenças Respiratórias
/
Neoplasias do Pulmão, Traqueia e Brônquios
Base de dados:
IBECS
Assunto principal:
Genes ras
/
Genes erbB-1
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Reação em Cadeia da Polimerase Via Transcriptase Reversa
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Linhagem Celular Tumoral
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Neoplasias Pulmonares
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Mutação
Tipo de estudo:
Estudo prognóstico
Limite:
Animais
/
Humanos
Idioma:
Inglês
Revista:
Clin. transl. oncol. (Print)
Ano de publicação:
2014
Tipo de documento:
Artigo
Instituição/País de afiliação:
University od Utah/USA
/
University of Utah/USA