{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T22:47:02Z","timestamp":1776120422296,"version":"3.50.1"},"reference-count":40,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2009,6,3]],"date-time":"2009-06-03T00:00:00Z","timestamp":1243987200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003074","name":"Agencia Nacional de Promoci\u00f3n Cient\u00edfica y Tecnol\u00f3gica","doi-asserted-by":"crossref","award":["PICT 2002 11944"],"award-info":[{"award-number":["PICT 2002 11944"]}],"id":[{"id":"10.13039\/501100003074","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003074","name":"Agencia Nacional de Promoci\u00f3n Cient\u00edfica y Tecnol\u00f3gica","doi-asserted-by":"crossref","award":["PICT 2006 02369"],"award-info":[{"award-number":["PICT 2006 02369"]}],"id":[{"id":"10.13039\/501100003074","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas de Argentina","award":["PEI 6557"],"award-info":[{"award-number":["PEI 6557"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Prostate"],"published-print":{"date-parts":[[2009,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Chronic inflammation has been postulated to be an important driving force to prostate carcinoma. Toll\u2010like receptors (TLRs) compose a family of receptors mainly expressed on immune cells. Recently, functional TLRs have been shown to be also expressed in numerous cancer cells, but their significance has only recently begun to be explored. The purpose of this study was to investigate the putative role of TLR4 expression in prostate carcinoma.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>To determine if there is an association between TLR4 expression and the malignancy of the tumor, 35 prostate carcinoma samples showing different Gleason grades were analyzed by immunohistochemistry. Also, to explore the functionality of the receptors expressed on the epithelium, we analyzed the type of cytokine response elicited and the signaling pathways involved after TLR4 triggering in the human prostate adenocarcinoma cell line, DU\u2010145.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>TLR4 is expressed in the normal prostate gland in both stroma and epithelium. TLR4 expression significantly drops to negative values as the Gleason grade augments in both, stroma and epithelium. Moreover, DU\u2010145 cells also exhibit TLR4 expression and respond to TLR4 agonists, activating the transcription factor NF\u2010\u03baB and increasing the expression of pro\u2010inflammatory mediators. Inhibition of the molecular adaptors MyD88 and MAL by overexpression of dominant\u2010negative mutants diminished LPS\u2010induced activation of NF\u2010\u03baB, showing that DU\u2010145 cells activate the NF\u2010\u03baB through MyD88\u2010dependent signaling pathways.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>We hypothesize that TLR4 in prostate cells could synergize with innate immune cells contributing to an eventual inflammatory process, which in genetically prone individuals could promote carcinogenesis. Prostate 69: 1387\u20131397, 2009. \u00a9 2009 Wiley\u2010Liss, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pros.20984","type":"journal-article","created":{"date-parts":[[2009,6,3]],"date-time":"2009-06-03T13:24:00Z","timestamp":1244035440000},"page":"1387-1397","source":"Crossref","is-referenced-by-count":54,"title":["Expression of Toll\u2010like receptor 4 in the prostate gland and its association with the severity of prostate cancer"],"prefix":"10.1002","volume":"69","author":[{"given":"Gerardo","family":"Gatti","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amado A.","family":"Quintar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Virginia","family":"Andreani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan 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