{"doi":"10.62347/xfot8509","title":"Retinoic acid receptor-β deletion in a model of early pancreatic ductal adenocarcinoma (PDAC) tumorigenesis","abstract":"Vitamin A (VA, retinol) and its metabolites, including retinoic acid (RA), play a major role in the maintenance of cell populations in the adult pancreas.Pancreatic ductal adenocarcinomas (PDACs) contain lower amounts of VA and express lower levels of retinoic acid receptors (RARs) compared to normal human pancreatic tissues.Our goal was to determine if VA signaling directly impacts molecular events underlying pancreatic carcinogenesis using cell-type specific genetic approaches in mice.We knocked out retinoic acid receptor beta (RAR-) selectively in pancreatic cells by tamoxifen treatment after crossing these adult RAR- fl/fl mice with Pdx1/CreER (PC er ) and lox-stop-lox KRas G12D transgenic mice.Our data show that the rounds of tamoxifen we used were able to induce the knockout of the RAR- gene in pancreatic cells in this PC er ;KRas;RAR- fl/fl transgenic model.We detected increases in proteins involved in RA metabolism (CYP26A1, RBP1, and ALDH1A2) in the PC er ;RAR- D/wt pancreata, but the levels of RBP1 and ALDH1A2 were decreased in PC er ;RAR- D (both RAR- alleles deleted) compared to PC er ;KRas;RAR- D and wildtype pancreata.Ki67 and vimentin proteins exhibited lower levels in the PC er ;KRas;RAR- D and PC er ;RAR- D pancreata compared to wild-type, indicating that deletion of RAR- reduced cell proliferation in acinar cells.Expression of SOX9, a key protein required for formation and maintenance of PDAC, was higher in PC er ;RAR- D/wt and PC er ;RAR- D pancreata compared to wild-type, indicating that deletion of RAR- increases SOX9 levels even without the KRas activating mutation.In summary, lack of RAR- in pancreatic acinar cells reduced cell proliferation and increased SOX9 protein levels in this transgenic model.","journal":"American Journal of Cancer Research","year":2025,"id":560730,"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":0.9629,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1429751,"name":"Eduardo Mere Del Aguila","orcid":"0000-0002-8746-657X","position":0,"is_corresponding":true}],"reference_count":58,"raw_metadata":null,"created_at":"2026-07-19T02:55:46.921885Z","pmid":"39949931","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":[]}