Glycine-N-methyltransferase and Malignant Diseases of the Prostate
Authors:
Z. Heger 1,2; T. Eckschlager 3; M. Stiborová 4; V. Adam 1,2
Authors place of work:
Ústav chemie a biochemie, Agronomická fakulta Mendelovy univerzity v Brně
1; CEITEC – Středoevropský technologický institut, VUT v Brně
2; Klinika dětské hematologie a onkologie 2. LF UK a FN v Motole, Praha
3; Katedra biochemie, Přírodovědecká fakulta UK v Praze
4
Published in the journal:
Klin Onkol 2016; 29(5): 331-335
Category:
Reviews
doi:
https://doi.org/10.14735/amko2016331
Summary
Background:
Prostate cancer (PC) constitutes a heterogeneous group of diseases with high prevalence rates that are still increasing, particularly in western countries. Since 1980, prostate specific antigen (PSA) and other diagnostic approaches have been used for PC screening; however, some of these approaches are often deemed painful and cause invasive damage of tissue. Therefore, molecular approaches to PC diagnosis are attracting increasing attention, potentially providing patients with less stressful situations and providing better diagnoses and even prognostic information. Recent metabolomic and genomic studies have suggested that biomolecules can be used as diagnostic or prognostic markers or as targets for the development of novel therapeutic modalities. One of these molecules is glycine-N-methyltransferase (GNMT), an enzyme that plays a pivotal role in the biochemical conversion of glycine to sarcosine. The link between this molecule (encoded by homonymous gene – GNMT) and PC has been confirmed at several levels, and thus GNMT can be considered a promising target for the development of advanced diagnostic and/or prognostic approaches.
Aim:
The aim of this study was to analyse the physiological role of GNMT and to examine in greater detail its connection with PC at different levels, including gene structure, gene expression, and metabolism, in which GNMT plays an important role, not only in controlling the methylation status of cells, but also the metabolism of folic acid and methionine. Last but not least, we discuss the importance of cellular methylation processes and the link between their aberrations and PC development.
Key words:
glycine – folic acid – metabolism – methylation – sarcosine
This work was supported by GA CR 16-18917S, League against Cancer Prague (project 2022015) and Czech Ministry of Health – RVO, UH Motol 00064203.
The authors declare they have no potential confl icts of interest concerning drugs, products, or services used in the study.
The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.
Submitted:
9. 2. 2016
Accepted:
20. 3. 2016
Zdroje
1. Rous P. Transmission of a malignant new growth by means of a cell-free filtrate. JAMA 1911; 56 (198): 1445–1446.
2. Baltimor D. RNA dependent DNA polymerase in virions of RNA tumor viruses. Nature 1970; 226 (5252): 1209–1211.
3. Croce CM. Oncogenes and cancer. N Engl J Med 2008; 358 (5): 502–511. doi: 10.1056/NEJMra072367.
4. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin 2016; 66 (1): 7–30. doi: 10.3322/caac.21332.
5. Abate-Shen C, Shen MM. Molecular genetics of prostate cancer. Genes Dev 2000; 14 (19): 2410–2434.
6. Warburg O. Origin of cancer cells. Science 1956; 123 (3191): 309–314.
7. Chen Z, Lu WQ, Garcia-Prieto C et al. The Warburg effect and its cancer therapeutic implications. J Bioenerg Biomembr 2007; 39 (3): 267–274.
8. Yeo EJ, Wagner C. Tissue distribution of glycine-N-methyltransferase, a major folate-binding protein of liver. Proc Natl Acad Sci U S A 1994; 91 (1): 210–214.
9. Chen YM, Chen LY, Wong FH et al. Genomic structure, expression, and chromosomal localization of the human glycine N-methyltransferase gene. Genomics 2000; 66 (1): 43–47.
10. Pattanayek R, Newcomer ME, Wagner C. Crystal structure of apo-glycine N-methyltransferase (GNMT). Protein Sci 1998; 7 (6): 1326–1331.
11. Krupenko NI, Wagner C. Transport of rat liver glycine N-methyltransferase into rat liver nuclei. J Biol Chem 1997; 272 (43): 27140–27146.
12. Kumar N, Kishore N. Structure and effect of sarcosine on water and urea by using molecular dynamics simulations: implications in protein stabilization. Biophys Chem 2013; 171 (1): 9–15. doi: 10.1016/j.bpc.2012.11. 004.
13. Cernei N, Heger Z, Gumulec J et al. Sarcosine as a potential prostate cancer biomarker – a review. Int J Mol Sci 2013; 14 (7): 13893–13908. doi: 10.3390/ijms140713 893.
14. Yen CH, Lin YT, Chen HL et al. The multi-functional roles of GNMT in toxicology and cancer. Toxicol Appl Pharmacol 2013; 266 (1): 67–75. doi: 10.1016/j.taap.2012.11. 003.
15. Liu SP, Li YS, Lee CM et al. Higher susceptibility to aflatoxin B-1-related hepatocellular carcinoma in glycine N-methyltransferase knockout mice. Int J Cancer 2011; 128 (3): 511–523. doi: 10.1002/ijc.25386.
16. Bhat R, Weaver JA, Wagner C et al. ATP depletion affects the phosphorylation state, ligand binding, and nuclear transport of the 4 S polycyclic aromatic hydrocarbon-binding protein in rat hepatoma cells. J Biol Chem 1996; 271 (51): 32551–32556.
17. Martinez-Chantar ML, Vazquez-Chantada M, Ariz U et al. Loss of the glycine N-methyltransferase gene leads to steatosis and hepatocellular carcinoma in mice. Hepatology 2008; 47 (4): 1191–1199. doi: 10.1002/hep.22 159.
18. Liao YJ, Liu SP, Lee CM et al. Characterization of a glycine N-methyltransferase gene knockout mouse model for hepatocellular carcinoma: Implications of the gender disparity in liver cancer susceptibility. Int J Cancer 2009; 124 (4): 816–826. doi: 10.1002/ijc.23979.
19. Huang YC, Lee CM, Chen M et al. Haplotypes, loss of heterozygosity, and expression levels of glycine N-methyltransferase in prostate cancer. Clin Cancer Res 2007; 13 (5): 1412–1420.
20. Ianni M, Porcellini E, Carbone I et al. Genetic factors regulating inflammation and DNA methylation associated with prostate cancer. Prostate Cancer Prostatic Dis 2013; 16 (1): 56–60. doi: 10.1038/pcan.2012. 30.
21. Gronberg H. Prostate cancer epidemiology. Lancet 2003; 361 (9360): 859–864.
22. Sreekumar A, Poisson LM, Rajendiran TM et al. Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature 2009; 457 (7231): 910–914. doi: 10.1038/nature07762.
23. Khan AP, Rajendiran TM, Ateeq B et al. The role of sarcosine metabolism in prostate cancer progression. Neoplasia 2013; 15 (5): 491–501.
24. Song YH, Shiota M, Kuroiwa K et al. The important role of glycine N-methyltransferase in the carcinogenesis and progression of prostate cancer. Mod Pathol 2011; 24 (9): 1272–1280. doi: 10.1038/modpathol.2011. 76.
25. Heger Z, Cernei N, Gumulec J et al. Determination of common urine substances as an assay for improving prostate carcinoma diagnostics. Oncol Rep 2014; 31 (4): 1846–1854. doi: 10.3892/or.2014.3054.
26. Burton C, Gamagedara S, Ma YF. A novel enzymatic technique for determination of sarcosine in urine samples. Anal Methods 2012; 4 (1): 141–146.
27. Wu H, Liu TT, Ma C et al. GC/MS-based metabolomic approach to validate the role of urinary sarcosine and target biomarkers for human prostate cancer by microwave-assisted derivatization. Anal Bioanal Chem 2011; 401 (2): 635–646. doi: 10.1007/s00216-011- 5098-9.
28. Cao DL, Ye DW, Zhang HL et al. A multiplex model of combining gene-based, protein-based, and metabolite-based with positive and negative markers in urine for the early diagnosis of prostate cancer. Prostate 2011; 71 (7): 700–710. doi: 10.1002/pros.21286.
29. Jentzmik F, Stephan C, Miller K et al. Sarcosine in urine after digital rectal examination fails as a marker in prostate cancer detection and identification of aggressive tumours. Eur Urol 2010; 58 (1): 12–18. doi: 10.1016/j.eururo.2010.01.035.
30. Suzuki MM, Bird A. DNA methylation landscapes: provocative insights from epigenomics. Nat Rev Genet 2008; 9 (6): 465–476. doi: 10.1038/nrg2341.
31. Kim JK, Samaranayake M, Pradhan S. Epigenetic mechanisms in mammals. Cell Mol Life Sci 2009; 66 (4): 596–612. doi: 10.1007/s00018-008-8432-4.
32. Goelz SE, Vogelstein B, Hamilton SR et al. Hypomethylation of DNA from benign and malignant human-colon neoplasms. Science 1985; 228 (4696): 187–190.
33. Clark SJ, Melki J. DNA methylation and gene silencing in cancer: which is the guilty party? Oncogene 2002; 21 (35): 5380–5387.
34. Saksouk N, Simboeck E, Dejardin J. Constitutive heterochromatin formation and transcription in mammals. Epigenetics Chromatin 2015; 8 (1): 3: doi: 10.1186/1756-8935-8-3.
35. Esteller M, Garcia-Foncillas J, Andion E et al. Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents. N Engl J Med 2000; 343 (19): 1350–1354.
36. Majumdar S, Buckles E, Estrada J et al. Aberrant DNA methylation and prostate cancer. Curr Genomics 2011; 12 (7): 486–505. doi: 10.2174/138920211797904061.
37. Hoque MO. DNA methylation changes in prostate cancer: current developments and future clinical implementation. Expert Rev Mol Diagn 2009; 9 (3): 243–257. doi: 10.1586/erm.09.10.
38. Delgado-Cruzata L, Hruby GW, Gonzalez K et al. DNA methylation changes correlate with gleason score and tumor stage in prostate cancer. DNA Cell Biol 2012; 31 (2): 187–192. doi: 10.1089/dna.2011.1311.
39. Dunn BK. Hypomethylation: one side of a larger picture. In: Verma M, Dunn BK, Umar A (eds). Epigenetics in cancer prevention: early detection and risk assessment. New York: New York Acad Sciences 2003: 28–42.
Štítky
Paediatric clinical oncology Surgery Clinical oncologyČlánok vyšiel v časopise
Clinical Oncology
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