Downregulation of GLS2 in glioblastoma cells is related to DNA hypermethylation but not to the p53 status

Molecular Carcinogenesis

Volumn 55, Issue 9, 2016, Pages 1309-1316

  Szeliga, Monika ^a   Bogacińska Karaś, Małgorzata ^a   Kuźmicz, Katarzyna ^b   Rola, Radosław ^c,d   Albrecht, Jan ^a  

^a MOSSAKOWSKI MEDICAL RESEARCH CENTRE   (Poland)

^b UNIVERSITY OF WARSAW   (Poland)

^c MEDICAL UNIVERSITY OF LUBLIN   (Poland)

^d INSTITUTE OF AGRICULTURAL MEDICINE   (Poland)

Author keywords

epigenetic silencing; glioblastoma; GLS2; TP53

Indexed keywords

DECITABINE; PROTEIN P53;

ARTICLE; CANCER CELL LINE; CONTROLLED STUDY; CPG ISLAND; DNA METHYLATION; DOWN REGULATION; EPIGENETICS; GENE EXPRESSION; GENE GLS2; GENE MUTATION; GENE SILENCING; GLIOBLASTOMA; HUMAN; HUMAN CELL; INTRON; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN CONTENT; TUMOR GENE;

EID: 84985028437     PISSN: 08991987     EISSN: 10982744     Source Type: Journal    
DOI: 10.1002/mc.22372     Document Type: Article

References (45)

1. Márquez J, Cardona C, Campos-Sandoval JA, et al. Mammalian glutaminase isozymes in brain. Metab Brain Dis 2013; 28:133–137.
2. Turner A, McGivan JD. Glutaminase isoform expression in cell lines derived from human colorectal adenomas and carcinomas. Biochem J 2003; 1:403–408.
3. Pérez-Gómez C, Campos-Sandoval JA, Alonso FJ, et al. Co-expression of glutaminase K and L isoenzymes in human tumour cells. Biochem J 2005; 15:535–542.
4. Márquez J, de la Oliva AR, Matés JM, Segura JA, Alonso FJ. Glutaminase: A multifaceted protein not only involved in generating glutamate. Neurochem Int 2006; 48:465–471.
5. Zhang J, Wang C, Chen M, et al. Epigenetic silencing of glutaminase 2 in human liver and colon cancers. BMC Cancer 2013; 13:601–609.
6. Hu W, Zhang C, Wu R, Sun Y, Levine A, Feng Z. Glutaminase 2, a novel p53 target gene regulating energy metabolism and antioxidant function. Proc Natl Acad Sci USA 2010; 107:7455–7460.
7. Szeliga M, Sidoryk M, Matyja E, Kowalczyk P, Albrecht J. Lack of expression of the liver-type glutaminase (LGA) mRNA in human malignant gliomas. Neurosci Lett 2005; 374:171–173.
8. Szeliga M, Obara-Michlewska M, Matyja E, et al. Transfection with liver-type glutaminase cDNA alters gene expression and reduces survival, migration and proliferation of T98G glioma cells. Glia 2009; 57:1014–1023.
9. Szeliga M, Zgrzywa A, Obara-Michlewska M, Albrecht J. Transfection of a human glioblastoma cell line with liver-type glutaminase (LGA) down-regulates the expression of DNA-repair gene MGMT and sensitizes the cells to alkylating agents. J Neurochem 2012; 123:428–436.
10. Ohgaki H, Kleihues P. Genetic profile of astrocytic and oligodendroglial gliomas. Brain Tumor Pathol 2011; 28:177–183.
11. Martín-Rufián M, Tosina M, Campos-Sandoval JA, et al. Mammalian glutaminase Gls2 gene encodes two functional alternative transcripts by a surrogate promoter usage mechanism. PLoS ONE 2012; 7:38380.
12. Martinez R, Esteller M. The DNA methylome of glioblastoma multiforme. Neurobiol Dis 2010; 39:40–46.
13. Liu J, Zhang C, Lin M, et al. Glutaminase 2 negatively regulates the PI3K/AKT signaling and shows tumor suppression activity in human hepatocellular carcinoma. Oncotarget 2014; 5:2635–2647.
14. Louis DN, Ohgaki H, Wiestler OD, et al. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 2007; 114:97–109.
15. Szeliga M, Matyja E, Obara M, Grajkowska W, Czernicki T, Albrecht J. Relative expression of mRNAS coding for glutaminase isoforms in CNS tissues and CNS tumors. Neurochem Res 2008; 33:808–813.
16. Li LC, Dahiya R. MethPrimer: Designing primers for methylation PCRs. Bioinformatics 2002; 18:1427–1431.
17. Hollstein M, Sidransky D, Vogelstein B, Harris CC. P53 mutations in human cancers. Science 1991; 253:49–53.
18. Fults D, Brockmeyer D, Tullous MW, Pedone CA, Cawthon RM. P53 mutation and loss of heterozygosity on chromosomes 17 and 10 during human astrocytoma progression. Cancer Res 1992; 52:674–679.
19. Anselmo NP, Rey JA, Almeida LO, et al. Concurrent sequence variation of TP53 and TP73 genes in anaplastic astrocytoma. Genet Mol Res 2009; 8:1257–1263.
20. Forbes SA, Beare D, Gunasekaran P, et al. COSMIC: Exploring the world's knowledge of somatic mutations in human cancer. Nucleic Acids Res 2015; 43:D805–D811.
21. Van Meir EG, Kikuchi T, Tada M, et al. Analysis of the p53 gene and its expression in human glioblastoma cells. Cancer Res 1994; 54:649–652.
22. Li H, Chen D, Zhang J. Analysis of intron sequence features associated with transcriptional regulation in human genes. PLoS ONE 2012; 7:46784.
23. Petitjean A, Mathe E, Kato S, et al. Impact of mutant p53 functional properties on TP53 mutation patterns and tumor phenotype: Lessons from recent developments in the IARC TP53 database. Hum Mutat 2007; 28:622–629.
24. Martín-Rufián M, Nascimento-Gomes R, Higuero A, et al. Both GLS silencing and GLS2 overexpression synergize with oxidative stress against proliferation of glioma cells. J Mol Med (Berl) 2014; 92:277–290.
25. Szeliga M, Albrecht J. Opposing roles of glutaminase isoforms in determining glioblastoma cell phenotype. Neurochem Int 2014; pii:S0197-0186 00230–7 doi: 10.1016/j.neuint.2014.11.004.
26. Gao P, Tchernyshyov I, Chang TC, et al. C-Myc suppression of miR-23a/b enhances mitochondrial glutaminase expression and glutamine metabolism. Nature 2009; 58:762–765.
27. Lobo C, Ruiz-Bellido MA, Aledo JC, Márquez J, Núñez De Castro I, Alonso FJ. Inhibition of glutaminase expression by antisense mRNA decreases growth and tumourigenicity of tumour cells. Biochem J 2000; 348:257–261.
28. Cheng T, Sudderth J, Yang C, et al. Pyruvate carboxylase is required for glutamine-independent growth of tumor cells. Proc Natl Acad Sci USA 2011; 108:8674–8679.
29. Qie S, Chu C, Li W, Wang C, Sang N. ErbB2 activation upregulates glutaminase 1 expression which promotes breast cancer cell proliferation. J Cell Biochem 2014; 115:498–509.
30. Seltzer MJ, Bennett BD, Joshi AD, et al. Inhibition of glutaminase preferentially slows growth of glioma cells with mutant I DH1. Cancer Res 2010; 70:8981–8987.
31. Wang JB, Erickson JW, Fuji R, et al. Targeting mitochondrial glutaminase activity inhibits oncogenic transformation. Cancer Cell 2010; 18:207–219.
32. Shukla K, Ferraris DV, Thomas AG, et al. Design, synthesis, and pharmacological evaluation of bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl) ethyl sulfide 3 (BPTES) analogs as glutaminase inhibitors. J Med Chem 2012; 55:10551–10563.
33. Lee YZ, Yang CW, Chang HY, et al. Discovery of selective inhibitors of Glutaminase-2, which inhibit mTORC1, activate autophagy and inhibit proliferation in cancer cells. Oncotarget 2014; 5:6087–6101.
34. Xiang L, Xie G, Liu C, et al. Knock-down of glutaminase 2 expression decreases glutathione, NADH, and sensitizes cervical cancer to ionizing radiation. Biochim Biophys Acta 2013; 1833:2996–3005.
35. Nakamura M, Yonekawa Y, Kleihues P, Ohgaki H. Promoter hypermethylation of the RB1 gene in glioblastomas. Lab Invest 2001; 81:77–82.
36. Baeza N, Weller M, Yonekawa Y, Kleihues P, Ohgaki H. PTEN methylation and expression in glioblastomas. Acta Neuropathol 2003; 106:479–485.
37. Amatya VJ, Naumann U, Weller M, Ohgaki H. TP53 promoter methylation in human gliomas. Acta Neuropathol 2005; 110:178–184.
38. Hegi ME, Diserens AC, Gorlia T, et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 2005; 352:997–1003.
39. Wiewrodt D, Nagel G, Dreimüller N, Hundsberger T, Perneczky A, Kaina B. MGMT in primary and recurrent human glioblastomas after radiation and chemotherapy and comparison with p53 status and clinical outcome. Int J Cancer 2008; 122:1391–1399.
40. Pavletich NP, Chambers KA, Pabo CO. The DNA-binding domain of p53 contains the four conserved regions and the major mutation hot spots. Genes Dev 1993; 7:2556–2564.
41. Lee DS, Yoon SY, Looi LM, et al. Comparable frequency of BRCA1, BRCA2 and TP53 germline mutations in a multi-ethnic Asian cohort suggests TP53 screening should be offered together with BRCA1/2 screening to early-onset breast cancer patients. Breast Cancer Res 2012; 14:R66.
42. Freed-Pastor WA, Prives C. Mutant p53: One name, many proteins. Genes Dev 2012; 26:1268–1286.
43. Giacobbe A, Bongiorno-Borbone L, Bernassola F, et al. P63 regulates glutaminase 2 expression. Cell Cycle 2013; 12:1395–1405.
44. Velletri T, Romeo F, Tucci P, et al. GLS2 is transcriptionally regulated by p73 and contributes to neuronal differentiation. Cell Cycle 2013; 12:3564–3573.
45. Watanabe T, Huang H, Nakamura M, et al. Methylation of the p73 gene in gliomas. Acta Neuropathol 2002; 104:357–362.