RESUMEN
Claudins are indispensible in modulating the permeability of epithelial and endothelial cells and in the maintenance of cell polarity. In order to verify the function of claudin-6 in the development of gastric cancer, we investigated claudin-6 expression in different gastric disease tissues. Moreover, we further explored whether overexpression of claudin-6 altered proliferation, apoptosis, migration, invasiveness, differentiation in BGC-823 cells and the potential mechanism. Immunohistochemistry was performed to detect the in situ expression of claudin-6 in different gastric disease tissues; moreover, cell culture, real-time PCR and western blot were used to evaluate the effect of overexpression of claudin-6 in vitro and the related mechanism. The results of immunohistochemical staining showed that the positivity of claudin-6 was significantly higher in superficial gastritis than that in gastric cancer. Overexpression of claudin-6 induced differentiation of BGC-823 cells by inhibiting the JNK pathway. However, it had no effect on proliferation, apoptosis, migration or invasiveness in vitro. The expression of claudin-6 was decreased in gastric cancer. Overexpression of claudin-6 induced differentiation of gastric cancer cells by inhibiting the JNK pathway.
Asunto(s)
Claudinas/metabolismo , Mucosa Gástrica/patología , Neoplasias Gástricas/patología , Diferenciación Celular , Línea Celular Tumoral , Regulación hacia Abajo , Femenino , Estudios de Seguimiento , Gastrectomía , Gastritis/patología , Gastroscopía , Humanos , Sistema de Señalización de MAP Quinasas , Masculino , Persona de Mediana Edad , Neoplasias Gástricas/cirugíaRESUMEN
Excision repair cross-complementing group 6 and 8 (ERCC6 and ERCC8) are two indispensable genes for the initiation of transcription-coupled nucleotide excision repair pathway. This study aimed to evaluate the interactions between single nucleotide polymorphisms of ERCC6 (rs1917799) and ERCC8 (rs158572 and rs158916) in gastric cancer and its precancerous diseases. Besides, protein level analysis were performed to compare ERCC6 and ERCC8 expression in different stages of gastric diseases, and to correlate SNPs jointly with gene expression. Sequenom MassARRAY platform method was used to detect polymorphisms of ERCC6 and ERCC8 in 1916 subjects. In situ ERCC6 and ERCC8 protein expression were detected by immunohistochemistry in 109 chronic superficial gastritis, 109 chronic atrophic gastritis and 109 gastric cancer cases. Our results demonstrated pairwise epistatic interactions between ERCC6 and ERCC8 SNPs that ERCC6 rs1917799-ERCC8 rs158572 combination was associated with decreased risk of chronic atrophic gastritis and increased risk of gastric cancer. ERCC6 rs1917799 also showed a significant interaction with ERCC8 rs158916 to reduce gastric cancer risk. The expressions of ERCC6, ERCC8 and ERCC6-ERCC8 combination have similarities that higher positivity was observed in chronic superficial gastritis compared with chronic atrophic gastritis and gastric cancer. As for the effects of ERCC6 and ERCC8 SNPs on the protein expression, single SNP had no correlation with corresponding gene expression, whereas the ERCC6 rs1917799-ERCC8 rs158572 pair had significant influence on ERCC6 and ERCC6-ERCC8 expression. In conclusion, ERCC6 rs1917799, ERCC8 rs158572 and rs158916 demonstrated pairwise epistatic interactions to associate with chronic atrophic gastritis and gastric cancer risk. The ERCC6 rs1917799-ERCC8 rs158572 pair significantly influence ERCC6 and ERCC6-ERCC8 expression.