PBX1 attributes as a determinant of connexin 32 downregulation in -related gastric carcinogenesis.

Aim: To clarify the mechanisms of connexin 32 (Cx32) downregulation by potential transcriptional factors (TFs) in ()-associated gastric carcinogenesis.

Methods: Approximately 25 specimens at each developmental stage of gastric carcinogenesis [non-atrophic gastritis, chronic atrophic gastritis, intestinal metaplasia, dysplasia and gastric carcinoma (GC)] with infection [ (+)] and 25 normal gastric mucosa (NGM) without infection [ (-)] were collected. After transcriptional factor array analysis, the Cx32 and PBX1 expression levels of -infected tissues from the developmental stages of GC and NGM with no infection were measured by real-time polymerase chain reaction (RT-PCR) and Western blot analysis. Regarding -infected animal models, the Cx32 and PBX1 mRNA expression levels and correlation between the gastric mucosa from 10 Mongolian gerbils with long-term colonization and 10 controls were analyzed. PBX1 and Cx32 mRNA and protein levels were further studied under the -infected condition as well as PBX1 overexpression and knockdown conditions .

Results: Incremental PBX1 was first detected by TF microarray in -related gastric carcinogenesis. The identical trend of PBX1 and Cx32 expression was confirmed in the developmental stages of -related clinical specimens. The negative correlation of PBX1 and Cx32 was confirmed in -infected Mongolian gerbils. Furthermore, decreased PBX1 expression was detected in the normal gastric epithelial cell line GES-1 with infection. Enforced overexpression or RNAi-mediated knockdown of PBX1 contributed to the diminished or restored Cx32 expression in GES-1 and the gastric carcinoma cell line BGC823, respectively. Finally, dual-luciferase reporter assay in HEK293T cells showed that Cx32 promoter activity decreased by 30% after PBX1 vector co-transfection, indicating PBX1 as a transcriptional downregulator of Cx32 by directly binding to its promoters.

Conclusion: PBX1 is one of the determinants in the Cx32 promoter targeting site, preventing further damage of gap junction protein in -associated gastric carcinogenesis.