| First Author | Soutto M | Year | 2015 |
| Journal | Oncotarget | Volume | 6 |
| Issue | 20 | Pages | 17911-22 |
| PubMed ID | 25980439 | Mgi Jnum | J:309318 |
| Mgi Id | MGI:6757312 | Doi | 10.18632/oncotarget.3772 |
| Citation | Soutto M, et al. (2015) Loss of TFF1 promotes Helicobacter pylori-induced beta-catenin activation and gastric tumorigenesis. Oncotarget 6(20):17911-22 |
| abstractText | Using in vitro and in vivo models, we investigated the role of TFF1 in suppressing H. pylori-mediated activation of oncogenic beta-catenin in gastric tumorigenesis. A reconstitution of TFF1 expression in gastric cancer cells decreased H. pylori-induced beta-catenin nuclear translocation, as compared to control (p < 0.001). These cells exhibited significantly lower beta-catenin transcriptional activity, measured by pTopFlash reporter, and induction of its target genes (CCND1 and c-MYC), as compared to control. Because of the role of AKT in regulating beta-catenin, we performed Western blot analysis and demonstrated that TFF1 reconstitution abrogates H. pylori-induced p-AKT (Ser473), p-beta-catenin (Ser552), c-MYC, and CCND1 protein levels. For in vivo validation, we utilized the Tff1-KO gastric neoplasm mouse model. Following infection with PMSS1 H. pylori strain, we detected an increase in the nuclear staining for beta-catenin and Ki-67 with a significant induction in the levels of Ccnd1 and c-Myc in the stomach of the Tff1-KO, as compared to Tff1-WT mice (p < 0.05). Only 10% of uninfected Tff1-KO mice, as opposed to one-third of H. pylori-infected Tff1-KO mice, developed invasive adenocarcinoma (p = 0.03). These findings suggest that loss of TFF1 could be a critical step in promoting the H. pylori-mediated oncogenic activation of beta-catenin and gastric tumorigenesis. |
