| First Author | Soutto M | Year | 2015 |
| Journal | Cancer | Volume | 121 |
| Issue | 24 | Pages | 4348-58 |
| PubMed ID | 26372254 | Mgi Jnum | J:320863 |
| Mgi Id | MGI:6880537 | Doi | 10.1002/cncr.29644 |
| Citation | Soutto M, et al. (2015) Trefoil factor 1 expression suppresses Helicobacter pylori-induced inflammation in gastric carcinogenesis. Cancer 121(24):4348-58 |
| abstractText | BACKGROUND: Infection with Helicobacter pylori, a high-risk factor for gastric cancer, is frequently associated with chronic inflammation through activation of nuclear factor kappaB (NF-kappaB). Trefoil factor 1 (TFF1) is a constitutively expressed protein in the stomach that has tumor-suppressor functions and plays a critical role in maintaining mucosal integrity. This study investigated the role of TFF1 in regulating the proinflammatory response to H. pylori infections. METHODS: For in vitro studies, immunofluorescence, luciferase reporter assays, Western blots, and quantitative real-time polymerase chain reaction were performed to investigate the activation of NF-kappaB and its target genes in response to infections with H. pylori strains J166 and 7.13. In addition, Tff1-knockout (KO) and Tff1-wild-type mice were used for infections with the H. pylori strain called premouse Sydney strain 1. RESULTS: The reconstitution of TFF1 expression in gastric cancer cells significantly suppressed H. pylori-mediated increases in NF-kappaB-p65 nuclear staining, transcriptional activity, and expression of proinflammatory cytokine genes (tumor necrosis factor alpha, interleukin 1beta, chemokine [C-X-C motif] ligand 5, and interleukin 4 receptor) that were associated with reductions in the expression and phosphorylation of NF-kappaB-p65 and IkappaB kinase alpha/beta proteins. The in vivo studies using the Tff1-KO mouse model of gastric neoplasia confirmed the in vitro findings. Furthermore, they demonstrated increases in chronic inflammation scores and in the frequency of invasive gastric adenocarcinoma in the Tff1-KO mice infected with H. pylori versus the uninfected Tff1-KO mice. CONCLUSIONS: These findings underscore an important protective role of TFF1 in abrogating H. pylori-mediated inflammation, a crucial hallmark of gastric tumorigenesis. Therefore, loss of TFF1 expression could be an important step in H. pylori-mediated gastric carcinogenesis. |
