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Int J Biochem Cell Biol ; 45(11): 2666-78, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24004834

RESUMO

Infection with Helicobacter pylori is important in the development and progression of gastric cancer. However, the mechanisms that regulate this activation in gastric tumors remain elusive. CACUL1 has been cloned and identified as a novel gene that is expressed in many types of cancer and is involved in cell cycle regulation and tumor growth. The current study aimed to examine the expression of CACUL1 in gastric cancer samples and analyze its correlation with H. pylori infection. We found that CACUL1 was highly expressed in gastric cancer tissues and negatively correlated with gastric cancer differentiation and TNM stage. In addition, CACUL1 expression was high in H. pylori-infected tissues compared with H. pylori non-infected tissue. We found that H. pylori could up-regulate CACUL1 expression through activating protein 1. The up-regulation of CACUL1 expression could promote matrix metalloproteinase 9 and Slug expression to increase invasion and metastasis of tumor cells. These results suggested that H. pylori-triggered CACUL1 production occurred in an activating protein 1-dependent manner and regulated matrix metalloproteinase 9 and Slug expression to affect the invasion and metastasis of tumor cells. Therefore, CACUL1 is a potential therapeutic target for the treatment of aggressive gastric cancer.


Assuntos
Proteínas Culina/genética , Helicobacter pylori/fisiologia , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/patologia , Fator de Transcrição AP-1/metabolismo , Regulação para Cima , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Antracenos/farmacologia , Linhagem Celular Tumoral , Proteínas Culina/metabolismo , Curcumina/farmacologia , Feminino , Mucosa Gástrica/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Pessoa de Meia-Idade , Invasividade Neoplásica , Metástase Neoplásica , Fosforilação , Regiões Promotoras Genéticas/genética , Proteínas Proto-Oncogênicas c-fos/metabolismo , Estômago/patologia , Neoplasias Gástricas/enzimologia , Neoplasias Gástricas/genética , Ativação Transcricional/genética , Adulto Jovem
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