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Based on analysis of genetically engineered mouse models combined with correlative analysis of expression profiling data from human prostate tumors, we demonstrate a reciprocal relationship between inflammation and the status of the NKX3.1 homeobox gene associated with prostate cancer initiation. We find that cancer initiation in aged Nkx3.1 mutant mice correlates with enrichment of specific immune populations and increased expression of immunoregulatory genes. Furthermore, expression of these immunoregulatory genes is similarly increased in human prostate tumors having low levels of NKX3.1 expression. We further show that induction of prostatitis in Nkx3.1 mutant mice accelerates prostate cancer initiation, which is coincident with aberrant cellular plasticity and differentiation. Correspondingly, human prostate tumors having low levels of NKX3.1 have de-regulated expression of genes associated with these cellular processes. We propose that loss of function of NKX3.1 accelerates inflammation-driven prostate cancer initiation potentially via aberrant cellular plasticity and impairment of cellular differentiation.<\/jats:p>\n               <jats:p>This article has an associated First Person interview with the first author of the paper.<\/jats:p>","DOI":"10.1242\/dmm.035139","type":"journal-article","created":{"date-parts":[[2018,9,28]],"date-time":"2018-09-28T12:45:53Z","timestamp":1538138753000},"source":"Crossref","is-referenced-by-count":34,"title":["Cooperation of loss of <i>NKX3.1<\/i> and inflammation in prostate cancer initiation"],"prefix":"10.1242","volume":"11","author":[{"given":"Cl\u00e9mentine","family":"Le Magnen","sequence":"first","affiliation":[{"name":"Institute of Cancer Genetics, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center 1 Departments of Medicine and Urology , , New York, NY 10032, \u2008 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renu K.","family":"Virk","sequence":"additional","affiliation":[{"name":"Columbia University Medical Center 2 Department of Pathology and Cell Biology , , NY 10032, \u2008 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aditya","family":"Dutta","sequence":"additional","affiliation":[{"name":"Institute of Cancer Genetics, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center 1 Departments of Medicine and Urology , , New York, NY 10032, \u2008 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaime Yeji","family":"Kim","sequence":"additional","affiliation":[{"name":"Herbert Irving Comprehensive Cancer Center 3 Department of Medicine , , , New York, NY 10032, \u2008 USA"},{"name":"Columbia University Medical Center 3 Department of Medicine , , , New York, NY 10032, \u2008 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sukanya","family":"Panja","sequence":"additional","affiliation":[{"name":"Rutgers School of Health Professions, Rutgers, The State University of New Jersey 4 Department of Health Informatics , , Newark, NJ 07101, \u2008 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoila A.","family":"Lopez-Bujanda","sequence":"additional","affiliation":[{"name":"Johns Hopkins University School of Medicine 5 Graduate Program in Pathobiology, Department of Pathology , , Baltimore, MD , USA"},{"name":"Columbia Center for Translational Immunology, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center 6 Department of Medicine , , New York, NY 10032, \u2008 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Califano","sequence":"additional","affiliation":[{"name":"Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center 7 Departments of Systems Biology and Biochemistry and Molecular Biophysics , , New York, NY 10032, \u2008 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles G.","family":"Drake","sequence":"additional","affiliation":[{"name":"Columbia Center for Translational Immunology, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center 6 Department of Medicine , , New York, NY 10032, \u2008 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonina","family":"Mitrofanova","sequence":"additional","affiliation":[{"name":"Rutgers School of Health Professions, Rutgers, The State University of New Jersey 4 Department of Health Informatics , , Newark, NJ 07101, \u2008 USA"},{"name":"Columbia University Medical Center 8 Department of Systems Biology , , New York, NY 10032, \u2008 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5021-0570","authenticated-orcid":false,"given":"Cory","family":"Abate-Shen","sequence":"additional","affiliation":[{"name":"Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center 9 Departments of Urology, Medicine, Pathology & Cell Biology, and Systems Biology , , New York, NY 10032, \u2008 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2018,11,16]]},"reference":[{"key":"2024061302123973100_DMM035139C1","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1111\/j.1432-0436.2008.00292.x","article-title":"Integrating differentiation and cancer: the Nkx3.1 homeobox gene in prostate organogenesis and carcinogenesis","volume":"76","author":"Abate-Shen","year":"2008","journal-title":"Differentiation"},{"key":"2024061302123973100_DMM035139C2","doi-asserted-by":"publisher","first-page":"174","DOI":"10.2174\/1874609810902030174","article-title":"Aging and inflammation: etiological culprits of cancer","volume":"2","author":"Ahmad","year":"2009","journal-title":"Curr. 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