DOI QR코드

DOI QR Code

Expression and Function of GSTA1 in Lung Cancer Cells

  • Pan, Xue-Diao ;
  • Yang, Zhou-Ping ;
  • Tang, Qi-Ling ;
  • Peng, Tong ;
  • Zhang, Zheng-Bing ;
  • Zhou, Si-Gui ;
  • Wang, Gui-Xiang ;
  • He, Bing ;
  • Zang, Lin-Quan
  • Published : 2014.11.06

Abstract

Glutathione S-transferase A1 (GSTA1) appears to be primarily involved in detoxification processes, but possible roles in lung cancer remain unclear. The objective of this study was to investigate the expression and function of GSTA1 in lung cancer cells. Real-time PCR and Western blotting were performed to assess expression in cancer cell lines and the normal lung cells, then verify the A549 cells line with stable overexpression. Localization of GSTA1 proteins was assessed by cytoimmunofluorescence. Three double-strand DNA oligoRNAs (SiRNAs) were synthesized prior to being transfected into A549 cells with Lipofectamine 2000, and then the most efficient SiRNA was selected. Expression of the GSTA1 gene in the transfected cells was determined by real-time PCR and Western blotting. The viability of the transfected cells were assessed by MTT. Results showed that the mRNA and protein expression of A549 cancer cells was higher than in MRC-5 normal cells. Cytoimmunofluorescence demonstrated GSTA1 localization in the cell cytoplasm and/or membranes. Transfection into A549 cells demonstrated that down-regulated expression could inhibit cell viability. Our data indicated that GSTA1 expression may be a target molecule in early diagnosis and treatment of lung cancer.

Keywords

GSTA1;A549;lung cancer;marker;target molecule

References

  1. Cho WC (2007). Potentially useful biomarkers for the diagnosis, treatment and prognosis of lung cancer. Biomed Pharmacother, 61, 515-9. https://doi.org/10.1016/j.biopha.2007.08.005
  2. Daorueang D, Thuwajit P, Roitrakul S, et al (2012). Secreted Opisthorchis viverrini glutathione S-transferase regulates cell proliferation through AKT and ERK pathways in cholangiocarcinoma. Parasitol Int, 61, 155-61. https://doi.org/10.1016/j.parint.2011.07.011
  3. Elbashir SM, Harborth J, Lendeckel W, et al (2001). Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature, 411, 494-8. https://doi.org/10.1038/35078107
  4. Hayes JD, Flanagan JU, Jowsey IR (2005). Glutathione transferases. Annu Rev Pharmacol Toxicol, 45, 51-88. https://doi.org/10.1146/annurev.pharmtox.45.120403.095857
  5. Hecht SS (2006). Cigarette smoking: cancer risks, carcinogens, and mechanisms. Langenbecks Arch Surg, 391, 603-13. https://doi.org/10.1007/s00423-006-0111-z
  6. Holley SL, Fryer AA, Haycock JW, et al (2007). Differential effects of glutathione S-transferase pi (GSTP1) haplotypes on cell proliferation and apoptosis. Carcinogenesis, 28, 2268-73. https://doi.org/10.1093/carcin/bgm135
  7. Khan MS, Khan MK, Siddiqui MH, Arif JM (2011). An in vivo and in silico approach to elucidate the tocotrienol-mediated fortification against infection and inflammation induced alterations in antioxidant defense system. Eur Rev Med Pharmacol Sci, 15, 916-30.
  8. Laborde E (2010). Glutathione transferases as mediators of signaling pathways involved in cell proliferation and cell death. Cell Death Differ, 17, 1373-80. https://doi.org/10.1038/cdd.2010.80
  9. Mannervik B, Board PG, Hayes JD, Listowsky I, Pearson WR (2005). Nomenclature for mammalian soluble glutathione transferases. Methods Enzymol, 401, 1-8. https://doi.org/10.1016/S0076-6879(05)01001-3
  10. Liang FQ, Alssadi R, Morehead P, Awasthi YC, Godley BF. (2005). Enhanced expression of glutathione-S-transferase A1-1 protects against oxidative stress in human retinal pigment epithelial cells. Exp Eye Res, 80, 113-119. https://doi.org/10.1016/j.exer.2004.08.017
  11. Balogh LM, Roberts AG, Shireman LM, Greene RJ, Atkins WM (2008). The stereochemical course of 4-hydroxy-2-nonenal metabolism by glutathione S-transferases. J Biol Chem, 283, 16702-10. https://doi.org/10.1074/jbc.M801725200
  12. Buccheri G, Torchio P, Ferrigno D (2003). Clinical equivalence of two cytokeratin markers in mon-small cell lung cancer: a study of tissue polypeptide antigen and cytokeratin 19 fragments. Chest, 124, 622-32. https://doi.org/10.1378/chest.124.2.622
  13. Molina R, Filella X, Auge JM (2004). ProGRP: a new biomarker for small cell lung cancer. Clin Biochem, 37, 505-11. https://doi.org/10.1016/j.clinbiochem.2004.05.007
  14. Oremek GM, Sauer-Eppel H, Bruzdziak TH (2007). Value of tumour and inflammatory markers in lung cancer. Anticancer Res, 27, 1911-5.
  15. Pollan M, Varela G, Torres A, et al (2003). Clinical value of p53, c-erbB-2, CEA and CA125 regarding relapse, metastasis and death in resectable non-small cell lung cancer. Int J Cancer, 107, 781-90. https://doi.org/10.1002/ijc.11472
  16. Siegel R, Naishadham D, Jemal A (2012). Cancer statistics, 2012. CA Cancer J Clin, 62, 10-29. https://doi.org/10.3322/caac.20138
  17. Sturgis EM, Cinciripini PM (2007). Trends in head and neck cancer incidence in relation to smoking prevalence: an emerging epidemic of human papillomavirus-associated cancers? Cancer, 110, 1429-35. https://doi.org/10.1002/cncr.22963
  18. Xie Q, Wang SC (2013). IL-33, an important biomarker in nonsmall-cell lung cancer? Asian Pac J Cancer Prev, 14, 7763. https://doi.org/10.7314/APJCP.2013.14.12.7763
  19. Zang L, Shi L, Guo J, et al (2009). Screening and identification of a peptide specifically targeted to NCI-H1299 from a phage display peptide library. Cancer Lett, 281, 64-70. https://doi.org/10.1016/j.canlet.2009.02.021

Cited by

  1. Human cytosolic glutathione-S-transferases: quantitative analysis of expression, comparative analysis of structures and inhibition strategies of isozymes involved in drug resistance vol.49, pp.3, 2017, https://doi.org/10.1080/03602532.2017.1343343
  2. RNAi-mediated gene silencing of vascular endothelial growth factor C suppresses growth and induces apoptosis in mouse breast cancer in vitro and in vivo vol.12, pp.5, 2016, https://doi.org/10.3892/ol.2016.5158
  3. GSTA1 Expression Is Correlated With Aldosterone Level in KCNJ5-Mutated Adrenal Aldosterone-Producing Adenoma vol.103, pp.3, 2017, https://doi.org/10.1210/jc.2017-00950
  4. Glutathione S-transferase A1 mediates nicotine-induced lung cancer cell metastasis by promoting epithelial-mesenchymal transition vol.14, pp.2, 2017, https://doi.org/10.3892/etm.2017.4663

Acknowledgement

Supported by : National Natural Science Foundation of China