{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T03:46:46Z","timestamp":1783568806725,"version":"3.55.0"},"reference-count":51,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T00:00:00Z","timestamp":1745884800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Secretar\u00eda de Ciencia, Humanidades, Tecnolog\u00eda e Innovaci\u00f3n (Secihti)","award":["A1-S-38213"],"award-info":[{"award-number":["A1-S-38213"]}]},{"name":"Secretar\u00eda de Ciencia, Humanidades, Tecnolog\u00eda e Innovaci\u00f3n (Secihti)","award":["CBF2023-2024-2470"],"award-info":[{"award-number":["CBF2023-2024-2470"]}]},{"name":"Secretar\u00eda de Ciencia, Humanidades, Tecnolog\u00eda e Innovaci\u00f3n (Secihti)","award":["09\/2019\/I"],"award-info":[{"award-number":["09\/2019\/I"]}]},{"name":"Secretar\u00eda de Ciencia, Humanidades, Tecnolog\u00eda e Innovaci\u00f3n (Secihti)","award":["08\/2017\/I"],"award-info":[{"award-number":["08\/2017\/I"]}]},{"DOI":"10.13039\/501100013394","name":"INMEGEN","doi-asserted-by":"publisher","award":["A1-S-38213"],"award-info":[{"award-number":["A1-S-38213"]}],"id":[{"id":"10.13039\/501100013394","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013394","name":"INMEGEN","doi-asserted-by":"publisher","award":["CBF2023-2024-2470"],"award-info":[{"award-number":["CBF2023-2024-2470"]}],"id":[{"id":"10.13039\/501100013394","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013394","name":"INMEGEN","doi-asserted-by":"publisher","award":["09\/2019\/I"],"award-info":[{"award-number":["09\/2019\/I"]}],"id":[{"id":"10.13039\/501100013394","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013394","name":"INMEGEN","doi-asserted-by":"publisher","award":["08\/2017\/I"],"award-info":[{"award-number":["08\/2017\/I"]}],"id":[{"id":"10.13039\/501100013394","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Prostate cancer (PCa) is a major global health concern, particularly in advanced stages where chemotherapy resistance and androgen-independent tumor growth reduce survival rates to below 30%. Toll-like receptor 3 (TLR3), regulated by tumor suppressor p53, is a promising therapeutic target due to its role in tumor cell apoptosis. However, chronic exposure to inorganic arsenic (iAs), a known carcinogen, has been linked to PCa progression and reduced TLR3 expression and activation by polyinosinic\/polycytidylic acid (Poly(I\/C)), a synthetic ligand used in PCa immunotherapy. Here, we demonstrate that chronic sodium arsenite (NaAsO) exposure increases p53 transcript and protein levels in immortalized prostate epithelial cells. Despite this, key p53 target genes, including TLR3, CDKN1A, and BAX, were significantly downregulated, indicating a transcriptionally inactive p53. Chromatin immunoprecipitation (ChIP) confirmed diminished p53 binding to TLR3 and CDKN1A promoters, while sequencing ruled out TP53 mutations. A bioinformatic analysis revealed elevated TP53 but reduced TLR3 and CDKN1A in prostate adenocarcinoma, suggesting that iAs-induced oxidative stress disrupts p53 function. These findings reveal a novel mechanism by which iAs promotes PCa progression through impaired p53 activity, highlighting the need to explore post-translational and epigenetic factors affecting p53. Restoring p53 transcriptional activity may offer a therapeutic strategy for PCa patients exposed to NaAsO.<\/jats:p>","DOI":"10.3390\/ijms26094253","type":"journal-article","created":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T05:50:17Z","timestamp":1745992217000},"page":"4253","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Inorganic Arsenic Induces Elevated p53 Levels with Altered Functionality Impacting the Expression of Toll-like Receptor 3 and Other Target Genes in Immortalized Prostate Epithelial Cells"],"prefix":"10.3390","volume":"26","author":[{"given":"Nancy C.","family":"Pacheco-Castillo","sequence":"first","affiliation":[{"name":"Laboratorio de Inmunotoxicolog\u00eda, Facultad de Ciencias Qu\u00edmicas, Universidad Aut\u00f3noma de San Luis Potos\u00ed, San Luis Potos\u00ed 78210, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7811-6415","authenticated-orcid":false,"given":"Jes\u00fas","family":"G\u00f3mez-Montalvo","sequence":"additional","affiliation":[{"name":"Consorcio de RNA, Laboratorio de Metabolismo de RNA Largos y Medicina Molecular, Instituto Nacional de Medicina Gen\u00f3mica, Ciudad de M\u00e9xico 14610, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanesa","family":"Olivares-Illana","sequence":"additional","affiliation":[{"name":"Laboratorio de Interacciones Biomoleculares y C\u00e1ncer, Instituto de F\u00edsica, Universidad Aut\u00f3noma de San Luis Potos\u00ed, San Luis Potos\u00ed 78210, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F\u00e9lix","family":"Recillas-Targa","sequence":"additional","affiliation":[{"name":"Instituto de Fisiolog\u00eda Celular, Departamento de Gen\u00e9tica Molecular, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Ciudad de M\u00e9xico 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1668-2830","authenticated-orcid":false,"given":"Erik J.","family":"Tokar","sequence":"additional","affiliation":[{"name":"Stem Cell Toxicology Group, Division of Translational Toxicology, National Institute of Environmental Health Science, Durham, NC 27709, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3188-924X","authenticated-orcid":false,"given":"S. Er\u00e9ndira","family":"Avenda\u00f1o-V\u00e1zquez","sequence":"additional","affiliation":[{"name":"Consorcio de RNA, Laboratorio de Metabolismo de RNA Largos y Medicina Molecular, Instituto Nacional de Medicina Gen\u00f3mica, Ciudad de M\u00e9xico 14610, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4597-1420","authenticated-orcid":false,"given":"Claudia","family":"Escudero-Lourdes","sequence":"additional","affiliation":[{"name":"Laboratorio de Inmunotoxicolog\u00eda, Facultad de Ciencias Qu\u00edmicas, Universidad Aut\u00f3noma de San Luis Potos\u00ed, San Luis Potos\u00ed 78210, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Vietri, M.T., D\u2019Elia, G., Caliendo, G., Resse, M., Casamassimi, A., Passariello, L., Albanese, L., Cioffi, M., and Molinari, A.M. (2021). 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