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GSTT1 is Deregulated in Left Colon Tumors

  • Coskunpinar, Ender (Department of Molecular Medicine, Institute of Experimental Medicine, Istanbul University) ;
  • Canbay, Emel (Kocaeli-Derince Education and Research Hospital) ;
  • Oltulu, Yasemin Musteri (Department of Molecular Medicine, Institute of Experimental Medicine, Istanbul University) ;
  • Tiryakioglu, Necip Ozan (Department of Molecular Medicine, Institute of Experimental Medicine, Istanbul University) ;
  • Bugra, Dursun (American Hospital, General Surgery Clinic)
  • Published : 2014.03.01

Abstract

Our aim was to determine GSTT1 expression levels in left colon tumors and paired normal tissue in order to identify specific alterations in GSTT1 mRNA levels. Alterations in GSTT1 expression in twenty-four left-sided colon tumors and paired cancer free tissue were determined by qRT-PCR. Significant fold changes were determined with t-test. When compared with cancer free tissue, left colon cancers showed a significant decrease in GSTT1 expression. However, GSTT1 mRNA levels among different grades increased gradually in correlation with tumor grade. Our results suggest that downregulation of GSTT1 in left-sided colon cancers is an early event and is reversed with cancer progression, probably due to cellular defense mechanisms as a response to changes in the microenvironment.

Keywords

References

  1. Chen S-H, Wu W-J, Tu H-P, et al (2013). Glutathione S-transferase expression in upper urinary tract urothelial carcinomas: a Taiwan study. Asian Pac J Cancer Prev, 14, 6475-9-84. https://doi.org/10.7314/APJCP.2013.14.11.6475
  2. Cotton SC, Sharp L, Little J, Brockton N (2000). Glutathione S-transferase polymorphisms and colorectal cancer: a huge review. Am J Epidemiol, 151, 7-32. https://doi.org/10.1093/oxfordjournals.aje.a010124
  3. de Bruin WC, Wagenmans MJ, Board PG, Peters WH (1999). Expression of glutathione S-transferase theta class isoenzymes in human colorectal and gastric cancers. Carcinogenesis, 20, 1453-7. https://doi.org/10.1093/carcin/20.8.1453
  4. Dialyna IA, Arvanitis DA, Spandidos DA (2001). Genetic polymorphisms and transcriptional pattern analysis of CYP1A1, AhR, GSTM1, GSTP1 and GSTT1 genes in breast cancer. Int J Mol Med, 8, 79-87.
  5. Diedrich A, Bock HC, Konig F, et al (2006). Expression of glutathione S-transferase T1 (GSTT1) in human brain tumours. Histol Histopathol, 21, 1199-207.
  6. Economopoulos KP, Sergentanis TN (2010). GSTM1, GSTT1, GSTP1, GSTA1 and colorectal cancer risk: a comprehensive meta-analysis. Eur J Cancer, 46, 1617-31. https://doi.org/10.1016/j.ejca.2010.02.009
  7. Ferlay J, Shin HR, Bray F, et al (2010). Colorectal cancer incidence, mortality and prevalence worldwide in 2008-summary. Available from: GLOBOCAN 2008 v2.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 10. Lyon, France: Int J Cancer, 127, 2893-917. https://doi.org/10.1002/ijc.25516
  8. Glebov OK, Rodriguez LM, Nakahara K, et al (2003). Distinguishing right from left colon by the pattern of gene expression. Cancer Epidemiol Biomarkers Prev, 12, 755-62.
  9. Grootjans J, Thuijls G, Verdam F, et al (2010). Non-invasive assessment of barrier integrity and function of the human gut. World J Gastrointest Surg, 2, 61.
  10. Ha YS, Yan C, Park C, et al (2011). GSTT1: a marker of the aggressiveness of bladder cancer. Urol Int, 86, 41-6. https://doi.org/10.1159/000321689
  11. Hayes JD, Pulford DJ (1995). The glutathione S-transferase supergene family: regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance. 18. Crit Rev Biochem Mol Biol, 30, 445-600. https://doi.org/10.3109/10409239509083491
  12. Ito M, Imai M, Muraki M, et al (2011). GSTT1 is upregulated by oxidative stress through p38-MK2 signaling pathway in human granulosa cells: possible association with mitochondrial activity. Aging, 3, 1213-23.
  13. Lee SA, Kim JW, Roh JW, et al (2004). Genetic polymorphisms of GSTM1, p21, p53 and HPV infection with cervical cancer in Korean women. Gynecol Oncol, 93, 14-8. https://doi.org/10.1016/j.ygyno.2003.11.045
  14. Mainwaring GW, Williams SM, Foster JR, Tugwood J, Green T (1996). The distribution of theta-class glutathione S-transferases in the liver and lung of mouse, rat and human. Biochem J, 318, 297-303.
  15. Mannervik, B (2012). Five decades with glutathione and the GSTome. J Biol Chem, 287, 6072-83. https://doi.org/10.1074/jbc.X112.342675
  16. Rotunno M, Lam TK, Vogt A, et al (2012). GSTM1 and GSTT1 copy numbers and mRNA expression in lung cancer. Mol Carcinog, 51, 142-50. https://doi.org/10.1002/mc.21890
  17. Singh H, Sachan R, Devi S, Pandey SN, Mittal B (2008). Association of GSTM1, GSTT1 and GSTM3 gene polymorphisms and susceptibility to cervical cancer in a North Indian population. Am J Obstet Gynecol, 198, 1-6. https://doi.org/10.1016/j.ajog.2007.11.031
  18. Sugai T, Habano W, Jiao YF, et al (2006). Analysis of molecular alterations in left-and right-sided colorectal carcinomas reveals distinct path ways of carcinogenesis: proposal for new molecular profile of colorectal carcinomas. J Mol Diagn, 8, 193-201. https://doi.org/10.2353/jmoldx.2006.050052
  19. Talalay P (2000). Chemoprotection against cancer by induction of phase 2 enzymes. Biofactors, 12, 5-11. https://doi.org/10.1002/biof.5520120102
  20. Tunali NE, Tiryakioglu NO (2011). Polymorphisms in the xenobiotic genes and susceptibility to bladder cancer. J Cell and Molecular Biology, 9, 5-13.
  21. van Eijl S, Zhu Z, Cupitt J, et al (2012). Elucidation of xenobiotic metabolism pathways in human skin and human skin models by proteomic profiling. PloS one, 7, 41721. https://doi.org/10.1371/journal.pone.0041721
  22. Whiteside TL (2008). The tumor microenvironment and its role in promoting tumor growth. Oncogene, 27, 5904-12. https://doi.org/10.1038/onc.2008.271
  23. Xu D, Yan S, Yin J, Zhang PN (2011). Null genotype of GSTT1 contributes to colorectal cancer risk in Asian populations: evidence from a meta-analysis. Asian Pac J Cancer Prev, 12, 2279-84.
  24. Yi SM, Li G-Y (2012). Null genotype of GSTT1 contributes to esophageal cancer risk in Asian populations: evidence from a meta-analysis Asian Pac J Cancer Prev, 13, 4967-71. https://doi.org/10.7314/APJCP.2012.13.10.4967
  25. Zhao Y, Marotta M, Eichler EE, Eng C, Tanaka H (2009). Linkage disequilibrium between two high-frequency deletion polymorphisms: implications for association studies involving the glutathione-S transferase (GST) genes. PLoS Genet, 5, 1000472. https://doi.org/10.1371/journal.pgen.1000472