{"doi":"10.17615/pnff-ec53","title":"K-ras Mutation Targeted to Gastric Tissue Progenitor Cells Results in Chronic Inflammation, an Altered Microenvironment, and Progression to Intraepithelial Neoplasia","abstract":"Chronic infectious diseases, such as Helicobacter pylori, can promote cancer in a large part through induction of chronic inflammation. Oncogenic K-Ras mutation in epithelial cells activates inflammatory pathways, which could compensate for a lack of infectious stimulus. Gastric histopathology and putative progenitor markers (Dcamkl1, Keratin 19) in Keratin 19-K-Ras-V12 (K19-kras) transgenic mice were assessed at 3, 6, 12 and 18 months of age, in comparison with Helicobacter felis (H. felis)-infected wild-type littermates. Inflammation was evaluated by RT-PCR of pro-inflammatory cytokines, and K19-kras mice were transplanted with GFP-labeled bone marrow. Both H. felis infection and kras mutation induced upregulation of pro-inflammatory cytokines, expansion of Dcamkl1+ cells, and progression to oxyntic atrophy, metaplasia, hyperplasia and high-grade dysplasia. K19-kras transgenic mice uniquely displayed mucous metaplasia as early as 3 months, and progressed to high-grade dysplasia and invasive intramucosal carcinoma by 20 months. In bone marrow transplanted K19-kras mice that progressed to dysplasia, a large proportion of stromal cells were GFP+ and bone marrow-derived, but only rare GFP+ epithelial cells were observed. GFP+ BMDCs included leukocytes and CD45− stromal cells that expressed vimentin or αSMA and were often found surrounding clusters of Dcamkl1+ cells at the base of gastric glands. In conclusions, the expression of mutant Kras in K19+ gastric epithelial cells can induce chronic inflammation and promote the development of dysplasia.","journal":"UNC Libraries","year":2020,"id":110835,"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":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9513,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":527927,"name":"Sophie S.W. Wang","orcid":null,"position":1,"is_corresponding":false},{"id":68288,"name":"Timothy C. Wang","orcid":"0000-0001-5730-3019","position":2,"is_corresponding":false},{"id":526975,"name":"Tomoyuki Okumura","orcid":"0000-0003-4952-5070","position":3,"is_corresponding":false},{"id":527928,"name":"Arlin B. Rogers","orcid":null,"position":4,"is_corresponding":false},{"id":527929,"name":"Kelly S. Betz","orcid":null,"position":5,"is_corresponding":false},{"id":526976,"name":"Shigeo Takaishi","orcid":"0000-0003-2236-6081","position":6,"is_corresponding":false},{"id":62839,"name":"James G. Fox","orcid":"0000-0001-9307-6116","position":7,"is_corresponding":false},{"id":526977,"name":"Wataru Shibata","orcid":"0000-0003-0326-6659","position":8,"is_corresponding":false},{"id":527930,"name":"Zinaida Dubeykovskiy","orcid":null,"position":9,"is_corresponding":false},{"id":35288,"name":"Anil K. Rustgi","orcid":"0000-0002-6439-6919","position":10,"is_corresponding":false},{"id":527931,"name":"Sureshkuma Muthupalani","orcid":null,"position":11,"is_corresponding":false},{"id":526974,"name":"Russell Ericksen","orcid":"0000-0001-6118-5131","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:13:01.914939Z","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":[]}