{"doi":"10.1158/0008-5472.c.6501212","title":"Data from K-ras Mutation Targeted to Gastric Tissue Progenitor Cells Results in Chronic Inflammation, an Altered Microenvironment, and Progression to Intraepithelial Neoplasia","abstract":"<div>Abstract<p>Chronic infectious diseases, such as <i>Helicobacter pylori</i> infection, 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 [doublecortin and calcium/calmodulin-dependent protein kinase-like 1 (Dcamkl1) and keratin 19 (K19)] in K19-K-ras-V12 (K19-kras) transgenic mice were assessed at 3, 6, 12, and 18 months of age, in comparison with <i>Helicobacter felis</i>–infected wild-type littermates. Inflammation was evaluated by reverse transcription–PCR of proinflammatory cytokines, and K19-kras mice were transplanted with green fluorescent protein (GFP)–labeled bone marrow. Both <i>H. felis</i> infection and K-ras mutation induced upregulation of proinflammatory cytokines, expansion of Dcamkl1<sup>+</sup> 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<sup>+</sup> and bone marrow–derived, but only rare GFP<sup>+</sup> epithelial cells were observed. GFP<sup>+</sup> bone marrow–derived cells included leukocytes and CD45<sup>−</sup> stromal cells that expressed vimentin or α smooth muscle actin and were often found surrounding clusters of Dcamkl1<sup>+</sup> cells at the base of gastric glands. In conclusion, the expression of mutant K-ras in K19<sup>+</sup> gastric epithelial cells can induce chronic inflammation and promote the development of dysplasia. Cancer Res; 70(21); 8435–45. ©2010 AACR.</p></div>","journal":null,"year":2023,"id":404327,"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":0.9495,"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":526974,"name":"Russell Ericksen","orcid":"0000-0001-6118-5131","position":1,"is_corresponding":false},{"id":526976,"name":"Shigeo Takaishi","orcid":"0000-0003-2236-6081","position":2,"is_corresponding":false},{"id":527927,"name":"Sophie S.W. Wang","orcid":null,"position":3,"is_corresponding":false},{"id":527930,"name":"Zinaida Dubeykovskiy","orcid":null,"position":4,"is_corresponding":false},{"id":526977,"name":"Wataru Shibata","orcid":"0000-0003-0326-6659","position":5,"is_corresponding":false},{"id":527929,"name":"Kelly S. Betz","orcid":null,"position":6,"is_corresponding":false},{"id":527931,"name":"Sureshkuma Muthupalani","orcid":null,"position":7,"is_corresponding":false},{"id":527928,"name":"Arlin B. Rogers","orcid":null,"position":8,"is_corresponding":false},{"id":62839,"name":"James G. Fox","orcid":"0000-0001-9307-6116","position":9,"is_corresponding":false},{"id":35288,"name":"Anil K. Rustgi","orcid":"0000-0002-6439-6919","position":10,"is_corresponding":false},{"id":68288,"name":"Timothy C. Wang","orcid":"0000-0001-5730-3019","position":11,"is_corresponding":false},{"id":526975,"name":"Tomoyuki Okumura","orcid":"0000-0003-4952-5070","position":0,"is_corresponding":true}],"reference_count":41,"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":[]}