Primary bile acid activates Egr1 expression through the MAPK signaling pathway in gastric cancer.
Mol Med Rep
; 25(4)2022 04.
Article
em En
| MEDLINE
| ID: mdl-35169855
ABSTRACT
Bile acids have been linked to pathomechanism and prognosis in various types of cancers. The present study aimed to investigate the effect of bile acids on the molecular change in gastric epithelial cancer cells and to evaluate gastric bile acid concentration in patients with early gastric cancer (EGC). Human gastric cancer cells (AGS and NCIN87 cell lines) were treated with several bile acid types to determine their effect on molecular changes in the cells. Gastric levels of individual bile acids were measured (primary unconjugated or conjugated bile acids and secondary bile acids) in 39 participants (20 controls and 19 patients with EGC). Exposing gastric epithelial cancer cells to primary bile acids in vitro upregulated the expression of early growth response factor 1 (Egr1) and the oncogenes including cJun, cMyc and Snail, whereas a p42/44 MAPK inhibitor exposure reduced their expression. There was a significant difference in age and presence of atrophic gastritis with intestinal metaplasia in background mucosa between controls and patients with EGC. There were significant differences in the levels of unconjugated or conjugated primary bile acids between controls and EGC patients except lithocholic acid. After adjustment of age and presence of atrophic gastritis with intestinal metaplasia, the levels of cholic acid [adjusted odds ratio (aOR) 4.3; 95% confidence interval (CI) 1.216.2; P=0.029] and glycochenodeoxycholic acid [aOR 9.9; 95% CI 1.375.3; P=0.027] were significantly higher in patients with EGC compared with controls. In conclusion, bile acids upregulate Egr1 in gastric cancer cells via the MAPK signaling pathway, and higher gastric levels of primary bile acids are associated with EGC. Therefore, exposure of gastric cells to primary bile acids may play a role in gastric carcinogenesis.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Gástricas
/
Ácidos e Sais Biliares
/
Proteína 1 de Resposta de Crescimento Precoce
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article