{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T12:40:06Z","timestamp":1751373606425,"version":"3.41.0"},"reference-count":53,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,5,11]],"date-time":"2025-05-11T00:00:00Z","timestamp":1746921600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Prostate"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>DNA hydroxymethylation (5hmC) is known to be altered in human prostate cancer. An animal model is required to study the functional roles of the ten eleven translocation (TET) DNA dioxygenases and the 5hmC modification in prostate cancer development and progression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We characterized Tet expression, global genomic 5hmC, and genome\u2010wide 5hmC patterns, and the transcriptome, in the TRansgenic Adenocarcinoma of Mouse Prostate (TRAMP) autochthonous model of prostate cancer.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We observed increased mRNA and protein levels of Tet1 in TRAMP samples, as compared to normal mouse prostate. Additionally, we found minimal expression of <jats:italic>Tet2<\/jats:italic> mRNA overall, and <jats:italic>Tet3<\/jats:italic> mRNA levels appeared similar in both sample types. However, TRAMP tumors expressed what appeared to be the inactive form of Tet3, versus the active form expressed in normal prostates. TRAMP tumors displayed global genomic hypohydroxymethylation (i.e., loss of 5hmC), and genome\u2010wide analysis revealed widespread hypohydroxymethylation was interspersed with regions of locus\u2010specific hyperhydroxymethylation (i.e., increased 5hmC). The differentially hydroxymethylated regions correlated with altered gene expression, and pathway analyses indicated that these genes often participate in oncogenic pathways.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Tet expression and 5hmC patterns are altered in the TRAMP model and closely match what has been observed in human prostate cancer, suggesting that TRAMP is a suitable model to study the role of Tets and 5hmC in prostate cancer development and progression.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pros.24912","type":"journal-article","created":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T04:08:47Z","timestamp":1747022927000},"page":"1036-1051","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Altered Ten Eleven Translocation Methylcytosine Dioxygenase Expression and DNA Hydroxymethylation in a Mouse Model of Prostate Cancer"],"prefix":"10.1002","volume":"85","author":[{"given":"Matthew","family":"Aguilera","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical and Administrative Sciences, College of Pharmacy and Health Sciences Western New England University Springfield Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David L.","family":"Klinkebiel","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Cell Biology, Fred &amp; Pamela Buffett Cancer Center University of Nebraska Medical Center Omaha Nebraska USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victoryn","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Administrative Sciences, College of Pharmacy and Health Sciences Western New England University Springfield Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey","family":"Rovatti","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Administrative Sciences, College of Pharmacy and Health Sciences Western New England University Springfield Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin","family":"Purizhansky","sequence":"additional","affiliation":[{"name":"Department of Pharmacology &amp; Therapeutics Roswell Park Comprehensive Cancer Center Buffalo New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara A.","family":"Foster","sequence":"additional","affiliation":[{"name":"Department of Pharmacology &amp; Therapeutics Roswell Park Comprehensive Cancer Center Buffalo New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam R.","family":"Karpf","sequence":"additional","affiliation":[{"name":"Fred &amp; Pamela Buffett Cancer Center, Eppley Institute University of Nebraska Medical Center Omaha Nebraska USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7120-7688","authenticated-orcid":false,"given":"Shannon R. 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