Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

Glutathione S-transferase polymorphisms: cancer incidence and therapy

Oncogene volume 25, pages 1639–1648 (2006)Cite this article

Abstract

The super family of glutathione S-transferases (GSTs) is composed of multiple isozymes with significant evidence of functional polymorphic variation. Over the last three decades, data from cancer studies have linked aberrant expression of GST isozymes with the development and expression of resistance to a variety of chemicals, including cancer drugs. This review addresses how differences in the human GST isozyme expression patterns influence cancer susceptibility, prognosis and treatment. In addition to the well-characterized catalytic activity, recent evidence has shown that certain GST isozymes can regulate mitogen-activated protein kinases or can facilitate the addition of glutathione to cysteine residues in target proteins (S-glutathionylation). These multiple functionalities have contributed to the recent efforts to target GSTs with novel small molecule therapeutics. Presently, at least two drugs are in late-stage clinical testing. The evolving functions of GST and their divergent expression patterns in individuals make them an attractive target for drug discovery.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  • Adler V, Yin Z, Fuchs SY, Benezra M, Rosario L, Tew KD et al. (1999). EMBO J 18: 1321–1334.

  • Alexandrie AK, Rannug A, Juronen E, Tasa G, Warholm M . (2002). Pharmacogenetics 12: 613–619.

  • Ali-Osman F, Akande O, Antoun G, Mao JX, Buolamwini J . (1997). J Biol Chem 272: 10004–10012.

  • Ambrosone CB, Sweeney C, Coles BF, Thompson PA, McClure GY, Korourian S et al. (2001). Cancer Res 61: 7130–7135.

  • Armstrong RN . (1997). Chem Res Toxicol 10: 2–18.

  • Baez S, Segura-Aguilar J, Widersten M, Johansson AS, Mannervik B . (1997). Biochem J 324 (Part 1): 25–28.

  • Bakker J, Lin X, Nelson WG . (2002). J Biol Chem 277: 22573–22580.

  • Beuckmann CT, Fujimori K, Urade Y, Hayaishi O . (2000). Neurochem Res 25: 733–738.

  • Blackburn AC, Coggan M, Tzeng HF, Lantum H, Polekhina G, Parker MW et al. (2001). Pharmacogenetics 11: 671–678.

  • Blackburn AC, Woollatt E, Sutherland GR, Board PG . (1998). Cytogenet Cell Genet 83: 109–114.

  • Board PG, Coggan M, Chelvanayagam G, Easteal S, Jermiin LS, Schulte GK et al. (2000). J Biol Chem 275: 24798–24806.

  • Cacciatore I, Caccuri AM, Cocco A, De Maria F, Di Stefano A, Luisi G et al. (2005). Amino Acids 29: 255–261.

  • Cho SG, Lee YH, Park HS, Ryoo K, Kang KW, Park J et al. (2001). J Biol Chem 276: 12749–12755.

  • Chuang ST, Chu P, Sugimura J, Tretiakova MS, Papavero V, Wang K et al. (2005). Am J Clin Pathol 123: 421–429.

  • Coggan M, Whitbread L, Whittington A, Board P . (1998). Biochem J 334 (Part 3): 617–623.

  • Coles B, Nowell SA, MacLeod SL, Sweeney C, Lang NP, Kadlubar FF . (2001). Mutat Res 482: 3–10.

  • Cowell IG, Dixon KH, Pemble SE, Ketterer B, Taylor JB . (1988). Biochem J 255: 79–83.

  • Dang DT, Chen F, Kohli M, Rago C, Cummins JM, Dang LH . (2005). Cancer Res 65: 9485–9494.

  • Davies SM, Robison LL, Buckley JD, Tjoa T, Woods WG, Radloff GA et al. (2001). J Clin Oncol 19: 1279–1287.

  • Davis Jr W, Ronai Z, Tew KD . (2001). J Pharmacol Exp Ther 296: 1–6.

  • DeJong JL, Mohandas T, Tu CP . (1991). Biochem Biophys Res Commun 180: 15–22.

  • Dirr H, Reinemer P, Huber R . (1994). Eur J Biochem 220: 645–661.

  • Dorion S, Lambert H, Landry J . (2002). J Biol Chem 277: 30792–30797.

  • Fernandez-Canon JM, Baetscher MW, Finegold M, Burlingame T, Gibson KM, Grompe M . (2002). Mol Cell Biol 22: 4943–4951.

  • Findlay VJ, Townsend DM, Saavedra JE, Buzard GS, Citro ML, Keefer LK et al. (2004). Mol Pharmacol 65: 1070–1079.

  • Gate L, Majumdar RS, Lunk A, Tew KD . (2004). J Biol Chem 279: 8608–8616.

  • Goto S, Iida T, Cho S, Oka M, Kohno S, Kondo T . (1999). Free Radic Res 31: 549–558.

  • Guo X, Dixit VS, Liu HP, Shroads AL, Henderson GN, James MO et al. (2005). Drug Metab Dispos: Epub ahead of print.

  • Hand PA, Inskip A, Gilford J, Alldersea J, Elexpuru-Camiruaga J, Hayes JD et al. (1996). Carcinogenesis 17: 1919–1922.

  • Hayes JD, Flanagan JU, Jowsey IR . (2005). Annu Rev Pharmacol Toxicol 45: 51–88.

  • Howells RE, Holland T, Dhar KK, Redman CW, Hand P, Hoban PR et al. (2001). Int J Gynecol Cancer 11: 107–112.

  • Howells RE, Redman CW, Dhar KK, Sarhanis P, Musgrove C, Jones PW et al. (1998). Clin Cancer Res 4: 2439–2445.

  • Ichijo H, Nishida E, Irie K, ten Dijke P, Saitoh M, Moriguchi T et al. (1997). Science 275: 90–94.

  • Inskip A, Elexperu-Camiruaga J, Buxton N, Dias PS, MacIntosh J, Campbell D et al. (1995). Biochem J 312 (Part 3): 713–716.

  • Johansson AS, Mannervik B . (2001). J Biol Chem 276: 33061–33065.

  • Lee WH, Morton RA, Epstein JI, Brooks JD, Campbell PA, Bova GS et al. (1994). Proc Natl Acad Sci USA 91: 11733–11737.

  • Lin X, Tascilar M, Lee WH, Vles WJ, Lee BH, Veeraswamy R et al. (2001). Am J Pathol 159: 1815–1826.

  • Liu J, Li C, Qu W, Leslie E, Bonifant CL, Buzard GS et al. (2004). Mol Cancer Ther 3: 709–714.

  • Lo HW, Ali-Osman F . (1998). Chem Biol Interact 111–112: 91–102.

  • Lohmueller KE, Pearce CL, Pike M, Lander ES, Hirschhorn JN . (2003). Nat Genet 33: 177–182.

  • Lyttle MH, Satyam A, Hocker MD, Bauer KE, Caldwell CG, Hui HC et al. (1994). J Med Chem 37: 1501–1507.

  • Manevich Y, Fisher AB . (2005). Free Radic Biol Med 38: 1422–1432.

  • Mannervik B, Danielson UH . (1988). CRC Crit Rev Biochem 23: 283–337.

  • Matthias C, Bockmuhl U, Jahnke V, Jones PW, Hayes JD, Alldersea J et al. (1998). Pharmacogenetics 8: 91–100.

  • Maugard CM, Charrier J, Pitard A, Campion L, Akande O, Pleasants L et al. (2001). Int J Cancer 91: 334–339.

  • McLellan RA, Oscarson M, Alexandrie AK, Seidegard J, Evans DA, Rannug A et al. (1997). Mol Pharmacol 52: 958–965.

  • Mondal BC, Paria N, Majumdar S, Chandra S, Mukhopadhyay A, Chaudhuri U et al. (2005). Eur J Cancer Prev 14: 281–284.

  • Morgan AS, Ciaccio PJ, Tew KD, Kauvar LM . (1996). Cancer Chemother Pharmacol 37: 363–370.

  • Morgan AS, Sanderson PE, Borch RF, Tew KD, Niitsu Y, Takayama T et al. (1998). Cancer Res 58: 2568–2575.

  • Nelson WG, De Marzo AM, Deweese TL, Lin X, Brooks JD, Putzi MJ et al. (2001). Ann NY Acad Sci 952: 135–144.

  • Ning B, Wang C, Morel F, Nowell S, Ratnasinghe DL, Carter W et al. (2004). Pharmacogenetics 14: 35–44.

  • O'Brien ML, Vulevic B, Freer S, Boyd J, Shen H, Tew KD . (1999). J Pharmacol Exp Ther 291: 1348–1355.

  • Pearson WR, Vorachek WR, Xu SJ, Berger R, Hart I, Vannais D et al. (1993). Am J Hum Genet 53: 220–233.

  • Pemble S, Schroeder KR, Spencer SR, Meyer DJ, Hallier E, Bolt HM et al. (1994). Biochem J 300 (Part 1): 271–276.

  • Ploemen JH, Van Schanke A, Van Ommen B, Van Bladeren PJ . (1994). Cancer Res 54: 915–919.

  • Ricci G, De Maria F, Antonini G, Turella P, Bullo A, Stella L et al. (2005). J Biol Chem 280: 26397–26405.

  • Rosario LA, O'Brien ML, Henderson CJ, Wolf CR, Tew KD . (2000). Mol Pharmacol 58: 167–174.

  • Ruscoe JE, Rosario LA, Wang T, Gate L, Arifoglu P, Wolf CR et al. (2001). J Pharmacol Exp Ther 298: 339–345.

  • Saitoh M, Nishitoh H, Fujii M, Takeda K, Tobiume K, Sawada Y et al. (1998). EMBO J 17: 2596–2606.

  • Seow HA, Penketh PG, Shyam K, Rockwell S, Sartorelli AC . (2005). Proc Natl Acad Sci USA 102: 9282–9287.

  • Smith CM, Kelsey KT, Wiencke JK, Leyden K, Levin S, Christiani DC . (1994). Cancer Epidemiol Biomarkers Prev 3: 471–477.

  • Smith G, Stanley LA, Sim E, Strange RC, Wolf CR . (1995). Cancer Surv 25: 27–65.

  • Stanulla M, Schrappe M, Brechlin AM, Zimmermann M, Welte K . (2000). Blood 95: 1222–1228.

  • Stoehlmacher J, Park DJ, Zhang W, Groshen S, Tsao-Wei DD, Yu MC et al. (2002). J Natl Cancer Inst 94: 936–942.

  • Strange RC, Fryer AA . (1999). IARC Sci Publ, 231–249.

  • Tan KL, Webb GC, Baker RT, Board PG . (1995). Genomics 25: 381–387.

  • Tanaka-Kagawa T, Jinno H, Hasegawa T, Makino Y, Seko Y, Hanioka N, Ando M . (2003). Biochem Biophys Res Commun 301: 516–520.

  • Tetlow N, Coggan M, Casarotto MG, Board PG . (2004a). Pharmacogenetics 14: 657–663.

  • Tetlow N, Robinson A, Mantle T, Board P . (2004b). Pharmacogenetics 14: 359–368.

  • Tew KD . (1994). Cancer Res 54: 4313–4320.

  • Tew KD, O'Brien M, Laing NM, Shen H . (1998). Chem Biol Interact 111–112: 199–211.

  • Tiltman AJ, Ali H . (2001). Histopathology 39: 266–272.

  • Townsend D, Tew K . (2003). Am J Pharmacogenomics 3: 157–172.

  • Townsend DM, Findlay VJ, Fazilev F, Ogle M, Fraser J, Saavedra J et al. (2005). Mol Pharmacol: Epub ahead of print.

  • Turella P, Cerella C, Filomeni G, Bullo A, De Maria F, Ghibelli L et al. (2005). Cancer Res 65: 3751–3761.

  • van der Logt EM, Bergevoet SM, Roelofs HM, van Hooijdonk Z, te Morsche RH, Wobbes T et al. (2004). Carcinogenesis 25: 2407–2415.

  • Wang L, Xu J, Ji C, Gu S, Lv Y, Li S et al. (2005). Int J Mol Med 16: 19–27.

  • Wang T, Arifoglu P, Ronai Z, Tew KD . (2001). J Biol Chem 276: 20999–21003.

  • Watson MA, Stewart RK, Smith GB, Massey TE, Bell DA . (1998). Carcinogenesis 19: 275–280.

  • Whitbread AK, Tetlow N, Eyre HJ, Sutherland GR, Board PG . (2003). Pharmacogenetics 13: 131–144.

  • Xu S, Wang Y, Roe B, Pearson WR . (1998). J Biol Chem 273: 3517–3527.

  • Ye Z, Song H . (2005). Eur J Cancer 41: 980–989.

  • Yengi L, Inskip A, Gilford J, Alldersea J, Bailey L, Smith A et al. (1996). Cancer Res 56: 1974–1977.

  • Yin Z, Ivanov VN, Habelhah H, Tew K, Ronai Z . (2000). Cancer Res 60: 4053–4057.

  • Yin ZL, Dahlstrom JE, Le Couteur DG, Board PG . (2001). J Histochem Cytochem 49: 983–987.

  • Zakharyan RA, Sampayo-Reyes A, Healy SM, Tsaprailis G, Board PG, Liebler DC et al. (2001). Chem Res Toxicol 14: 1051–1057.

Download references

Acknowledgements

This publication was made possible by grant number NCI CA53783 from the National Institutes of Health and grant number T32 ES012878 from the National Institutes of Environmental Health Sciences, NIH.

Author information

Authors and Affiliations

  1. Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, SC, USA

    C C McIlwain, D M Townsend & K D Tew

Authors
  1. C C McIlwain
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. D M Townsend
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. K D Tew
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to K D Tew.

Rights and permissions

Reprints and permissions

About this article

Cite this article

McIlwain, C., Townsend, D. & Tew, K. Glutathione S-transferase polymorphisms: cancer incidence and therapy. Oncogene 25, 1639–1648 (2006). https://doi.org/10.1038/sj.onc.1209373

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1209373

Keywords

This article is cited by

Search

Advanced search

Quick links