{"doi":"10.1158/0008-5472.c.6494573","title":"Data from Balance between Polyoma Enhancing Activator 3 and Activator Protein 1 Regulates <i>Helicobacter pylori</i>–Stimulated Matrix Metalloproteinase 1 Expression","abstract":"<div>Abstract<p><i>Helicobacter pylori</i> infection and elevated expression of tissue matrix metalloproteinase 1 (MMP-1) are both associated with gastric cancer. We investigated the regulation of MMP-1 expression during <i>H. pylori</i> infection. Real-time reverse transcription-PCR was used to examine mucosal MMP-1 mRNA levels in 55 patients with gastric cancers and 61 control patients. Increased MMP-1 mRNA levels in the gastric mucosa and epithelial cells were observed in <i>H. pylori</i> infections in which both the <i>cag</i> pathogenicity island (PAI) and outer inflammatory protein A (OipA) were expressed. The combined induction of <i>c-fos, c-jun</i>, and polyoma enhancing activator-3 (<i>pea-3</i>) by <i>H. pylori</i> caused maximal increase in MMP-1 expression. Activation of the MMP-1 promoter by <i>H. pylori</i> involved occupation of the activator protein 1 (AP-1) sites at −72 and −181 and, surprisingly, vacancy of the −88 PEA-3 site. Electrophoretic mobility shift, supershift, and chromatin immunoprecipitation assays showed increased binding of c-Fos and c-Jun to the −72 and −181 AP-1 sites during <i>H. pylori</i> infection. Importantly, during wild-type <i>H. pylori</i> infection, we detected increased PEA-3 binding to the −72AP-1 site and decreased PEA-3 binding to the −88 PEA-3 site. However, during infection with the <i>cag</i> PAI and <i>oipA</i> mutants, PEA-3 binding to the −88 site was detected. MMP-1 and <i>pea-3</i> activities are increased in gastric cancers. Maximal activation of MMP-1 transcription requires the <i>cag</i> PAI and OipA, which regulate AP-1 and PEA-3 binding. Thus, <i>cag</i> PAI and OipA provide a possible link between bacterial virulence factors and important host factors related to disease pathogenesis. (Cancer Res 2006; 66(10): 5111-20)</p></div>","journal":null,"year":2023,"id":404274,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9552,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":543893,"name":"Hong Lu","orcid":"0000-0001-7267-0765","position":1,"is_corresponding":false},{"id":1182201,"name":"Yubo Sun","orcid":"0000-0002-3475-9723","position":2,"is_corresponding":false},{"id":270539,"name":"David Y. Graham","orcid":"0000-0002-6908-8317","position":3,"is_corresponding":false},{"id":1182197,"name":"Herman S. Cheung","orcid":null,"position":4,"is_corresponding":false},{"id":312531,"name":"Yoshio Yamaoka","orcid":"0000-0002-1222-5819","position":5,"is_corresponding":false},{"id":1182196,"name":"Jeng Yih Wu","orcid":null,"position":0,"is_corresponding":true}],"reference_count":27,"raw_metadata":null,"created_at":"2026-07-19T01:20:44.591715Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}