PMID- 25901741 OWN - NLM STAT- MEDLINE DCOM- 20160308 LR - 20200930 IS - 1555-8576 (Electronic) IS - 1538-4047 (Print) IS - 1538-4047 (Linking) VI - 16 IP - 6 DP - 2015 TI - GATA-3 augmentation down-regulates Connexin43 in Helicobacter pylori associated gastric carcinogenesis. PG - 987-96 LID - 10.1080/15384047.2015.1030552 [doi] AB - Helicobacter pylori (H. pylori) is a risk factor of gastric carcinoma, and inflammation with H.pylori infection has widely been suggested to trigger gastric carcinogenesis through "inflammation-carcinoma chain" (non-atrophic gastritis (NAG) --> chronic atrophic gastritis (CAG) --> intestinal metaplasia (IM) --> dysplasia (DYS) and gastric carcinoma (GC)). Connexin43 (Cx43) is a major constituent of gap junction in normal gastric mucosa (NGM) and it is continuously down-regulated from normal gastric mucosa to precancerous lesions or ultimate gastric carcinoma, which shows novel target against gastric carcinoma by preventing the Cx43 decline. Our previous studies demonstrated that H. pylori infection in gastric mucosa down-regulates Cx43 expression, but its mechanism remains unknown. The transcriptional factor, GATA binding protein 3 (GATA-3) is the key to regulate adaptive immune response, which possibly relates to inflammation toward malignant transformation. Here the substantial rising of GATA-3 was screened by transcriptional factor microarray along the developmental stages of H. pylori associated gastric carcinoma. Moreover, the increased GATA-3 and inhibited Cx43 were confirmed in clinical specimens, Mongolian gerbils and normal gastric epithelial cell line GES-1 with H. pylori infection. GATA-3 silencing generated the Cx43 restoration both in intermediate differentiation gastric cancer cells BGC-803 and in H. pylori infected GES-1 cells. Dual-luciferase reporter assay further revealed the GATA-3 as one of Cx43 down-regulators by directly binding to its promoters. Together, the incremental GATA-3 is found in H. pylori associated gastric carcinogenesis, which is responsible for Cx43 inhibition as well. FAU - Liu, Xiaoming AU - Liu X AD - a Department of Gastroenterology ; Third Xiangya Hospital ; Central South University ; Changsha , PR China. FAU - Cao, Ke AU - Cao K FAU - Xu, Canxia AU - Xu C FAU - Hu, Tingzi AU - Hu T FAU - Zhou, Li AU - Zhou L FAU - Cao, Dan AU - Cao D FAU - Xiao, Jing AU - Xiao J FAU - Luo, Ling AU - Luo L FAU - Guo, Yinjie AU - Guo Y FAU - Qi, Yong AU - Qi Y LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150422 PL - United States TA - Cancer Biol Ther JT - Cancer biology & therapy JID - 101137842 RN - 0 (Connexin 43) RN - 0 (GATA3 Transcription Factor) RN - 0 (Transcription Factors) SB - IM MH - Animals MH - Cell Line, Tumor MH - *Cell Transformation, Neoplastic MH - Connexin 43/*genetics MH - Disease Models, Animal MH - GATA3 Transcription Factor/*genetics MH - Gastric Mucosa/metabolism/microbiology/pathology MH - Gene Expression Profiling MH - *Gene Expression Regulation, Neoplastic MH - Gerbillinae MH - Helicobacter Infections/*complications/*microbiology MH - *Helicobacter pylori MH - Humans MH - Promoter Regions, Genetic MH - Protein Binding MH - Stomach Neoplasms/*etiology/pathology MH - Transcription Factors/metabolism PMC - PMC4622629 OTO - NOTNLM OT - CAG, chronic atrophic gastritis OT - CagA, cytotoxin-associated gene A OT - Connexin43 OT - Cx43, connexin43 OT - DYS, dysplasia OT - GATA-3 OT - GATA-3, GATA binding protein 3 OT - GC, gastric carcinoma OT - GJ, gap junction OT - H. pylori, Helicobacter pylori OT - Helicobacter pylori OT - IFN-gamma, interferon-gamma OT - ILC, innate lymphoid cell OT - IM, intestinal metaplasia OT - NAG, non-atrophic gastritis OT - NGM, normal gastric mucosa. OT - PBMC, peripheral blood mononuclear cell OT - PBS, phosphate buffered saline OT - TF, transcriptional factor OT - Th1/Th2 cell, type 1/2 T helper cell OT - VacA, vacuolating cytotoxin gene A OT - carcinogenesis OT - gastric carcinoma OT - inflammation-carcinoma chain OT - transcription factor EDAT- 2015/04/23 06:00 MHDA- 2016/03/10 06:00 PMCR- 2016/04/22 CRDT- 2015/04/23 06:00 PHST- 2015/04/23 06:00 [entrez] PHST- 2015/04/23 06:00 [pubmed] PHST- 2016/03/10 06:00 [medline] PHST- 2016/04/22 00:00 [pmc-release] AID - 1030552 [pii] AID - 10.1080/15384047.2015.1030552 [doi] PST - ppublish SO - Cancer Biol Ther. 2015;16(6):987-96. doi: 10.1080/15384047.2015.1030552. Epub 2015 Apr 22.