Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 1 de 1
Filtrar
Mais filtros

Base de dados
Ano de publicação
Tipo de documento
País de afiliação
Intervalo de ano de publicação
1.
Cell Physiol Biochem ; 35(3): 983-96, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25660117

RESUMO

BACKGROUND & AIMS: To investigate the expression and prognostic value of MACC1 in patients with HCC and identify the mechanism by which MACC1 inhibits HCC cell apoptosis. METHODS: MACC1 and p-AKT expression was studied using immunohistochemistry of both HCC tissues and adjacent liver tissues. qRT-PCR and western immunoblotting were used to examine the expression of target genes at the mRNA and protein levels, respectively. The MTT assay was used to assess cell viability, and cell apoptosis was determined by DAPI staining, Annexin V/PI staining and Caspase 3/7 assay. Nude mice were used to perform in vivo experiments. RESULTS: The overexpression of MACC1 was found in HCC tissues and was correlated with poor postsurgical prognosis. There was a positive relationship between MACC1 and p-AKT expression in HCC tissues. In vitro experiments showed that MACC1 repressed HCC cell apoptosis and promoted cell growth. Knockdown of c-MET abolished the anti-apoptotic function of MACC1. Next, MACC1 was verified to activate PI3K/AKT signaling by sensitizing HGF/c-MET signaling in HCC. MACC1 overexpression enhanced the HGF-driven phosphorylation of BAD, Caspase 9 and FKHRL1 and inhibited their pro-apoptotic functions in HCC cells. Finally, MACC1 was shown to inhibit cell apoptosis and promote HCC growth in vivo. CONCLUSIONS: This investigation revealed that MACC1 overexpression predicted worse prognosis after liver resection, which was attributed to the repression of HCC cell apoptosis via a molecular mechanism in which MACC1 accelerated the activation of the HGF/c-MET/PI3K/AKT pathway and phosphorylated BAD, Caspase 9 and FKHRL1, ultimately preventing their nuclear translocation and their pro-apoptotic function.


Assuntos
Carcinoma Hepatocelular/genética , Fator de Crescimento de Hepatócito/biossíntese , Neoplasias Hepáticas/genética , Proteína Oncogênica v-akt/biossíntese , Proteínas Proto-Oncogênicas c-met/genética , Fatores de Transcrição/biossíntese , Animais , Apoptose , Carcinoma Hepatocelular/patologia , Caspase 9/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Proteína Forkhead Box O3 , Fatores de Transcrição Forkhead/metabolismo , Regulação Neoplásica da Expressão Gênica , Fator de Crescimento de Hepatócito/genética , Xenoenxertos , Humanos , Neoplasias Hepáticas/patologia , Camundongos , Proteína Oncogênica v-akt/genética , Fosfatidilinositol 3-Quinases/genética , RNA Mensageiro , Transdução de Sinais , Transativadores , Fatores de Transcrição/genética , Proteína de Morte Celular Associada a bcl/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA