{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T21:29:10Z","timestamp":1788298150431,"version":"build-2803163510"},"reference-count":36,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,10,18]],"date-time":"2021-10-18T00:00:00Z","timestamp":1634515200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Prostate"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Metabolic reprograming is now a recognized hallmark of cancer. The prostate\u2010specific phosphatase and tensin homolog deleted on chromosome 10 (<jats:italic>Pten<\/jats:italic>) gene\u2010conditional knockout (KO) mouse carcinogenesis model is highly desirable for studying prostate cancer biology and prevention due to its close resemblance of primary molecular defects and histopathological features of human prostate cancer. We have recently published macromolecular profiling of this model by proteomics and transcriptomics, denoting a preeminence of inflammation and myeloid suppressive immune cell features. Here, we performed metabolomic analyses of <jats:italic>Pten<\/jats:italic>\u2010KO prostate versus wild type (WT) counterpart for discernable changes in the aqueous metabolites and contrasted to those in the TRAMP neuroendocrine carcinoma (NECa).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Three matched pairs of tissue\u2010specific conditional <jats:italic>Pten<\/jats:italic>\u2010KO mouse prostate and WT prostate of litter\/cage\u2010mates at 20\u201322 weeks of age and three pairs of TRAMP NECa versus WT (28\u201331 weeks) were profiled for their global aqueous metabolite changes, using hydrophilic interaction liquid chromatography\u2010tandem mass spectrometry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The <jats:italic>Pten<\/jats:italic>\u2010KO prostate increased purine nucleotide pools, cystathionine, and both reduced and oxidized glutathione (GSH, GSSG), and gluconate\/glucuronate species in addition to cholesteryl sulfate and polyamine precursor ornithine. On the contrary, <jats:italic>Pten<\/jats:italic>\u2010KO prostate contained diminished pools of glycolytic intermediates and phosphorylcholine derivatives, select amino acids, and their metabolites. Bioinformatic integration revealed a significant shunting of glucose away from glycolysis\u2010citrate cycle and glycerol\u2010lipid genesis to pentose phosphate cycle for NADPH\/GSH\/GSSG redox and pentose moieties for purine and pyrimidine nucleotides, and glycosylation\/glucuronidation. Implicit arginine catabolism to ornithine was consistent with immunosuppression in <jats:italic>Pten<\/jats:italic>\u2010KO model. While also increased in cystathionine\u2010GSH\/GSSG, purine, and pyrimidine nucleotide pools and glucuronidation at the expense of glycolysis\u2010citrate cycle, the TRAMP NECa increased abundance of many amino acids, methyl donor S\u2010adenosyl\u2010methionine, and intermediates for phospholipids without increasing cholesteryl sulfate or ornithine.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The aqueous metabolomic patterns in <jats:italic>Pten<\/jats:italic>\u2010KO prostate and TRAMP NECa shared similarities in the greater pools of cystathionine, GSH\/GSSG redox pair, and nucleotides and shunting away from glycolysis\u2010citrate cycle in both models. Remarkable metabolic distinctions between them included metabolisms of many amino acids (protein synthesis; arginine\u2010ornithine\/immune suppression) and cholesteryl sulfate and methylation donor for epigenetic regulations.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pros.24256","type":"journal-article","created":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T21:50:43Z","timestamp":1634766643000},"page":"154-166","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Aqueous metabolome of tissue\u2010specific conditional <i>Pten<\/i>\u2010knockout mouse prostate cancer and TRAMP neuroendocrine carcinoma"],"prefix":"10.1002","volume":"82","author":[{"given":"Sangyub","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Pharmacology Pennsylvania State University College of Medicine Hershey Pennsylvania 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