Academic Journal
Aqueous metabolome of tissue‐specific conditional Pten‐knockout mouse prostate cancer and TRAMP neuroendocrine carcinoma
| العنوان: | Aqueous metabolome of tissue‐specific conditional Pten‐knockout mouse prostate cancer and TRAMP neuroendocrine carcinoma |
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| المؤلفون: | Kim, Sangyub, Li, Li, Zhang, Jinhui, Jiang, Cheng, Lü, Junxuan |
| المصدر: | The Prostate ; volume 82, issue 1, page 154-166 ; ISSN 0270-4137 1097-0045 |
| بيانات النشر: | Wiley |
| سنة النشر: | 2021 |
| المجموعة: | Wiley Online Library (Open Access Articles via Crossref) |
| الوصف: | Background Metabolic reprograming is now a recognized hallmark of cancer. The prostate‐specific phosphatase and tensin homolog deleted on chromosome 10 ( Pten ) gene‐conditional 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 Pten ‐KO prostate versus wild type (WT) counterpart for discernable changes in the aqueous metabolites and contrasted to those in the TRAMP neuroendocrine carcinoma (NECa). Methods Three matched pairs of tissue‐specific conditional Pten ‐KO mouse prostate and WT prostate of litter/cage‐mates at 20–22 weeks of age and three pairs of TRAMP NECa versus WT (28–31 weeks) were profiled for their global aqueous metabolite changes, using hydrophilic interaction liquid chromatography‐tandem mass spectrometry. Results The Pten ‐KO 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, Pten ‐KO 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‐citrate cycle and glycerol‐lipid 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 Pten ‐KO model. While also increased in cystathionine‐GSH/GSSG, purine, and pyrimidine nucleotide pools and glucuronidation at ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1002/pros.24256 |
| الاتاحة: | http://dx.doi.org/10.1002/pros.24256 https://onlinelibrary.wiley.com/doi/pdf/10.1002/pros.24256 https://onlinelibrary.wiley.com/doi/full-xml/10.1002/pros.24256 |
| Rights: | http://creativecommons.org/licenses/by-nc/4.0/ |
| رقم الانضمام: | edsbas.608E4F62 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1002/pros.24256 |
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