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.

  • Original Paper
  • Published:

Detailed methylation analysis of the glutathione S-transferase π (GSTP1) gene in prostate cancer

Oncogene volume 18, pages 1313–1324 (1999)Cite this article

Abstract

Glutathione-S-Transferases (GSTs) comprise a family of isoenzymes that provide protection to mammalian cells against electrophilic metabolites of carcinogens and reactive oxygen species. Previous studies have shown that the CpG-rich promoter region of the π-class gene GSTP1 is methylated at single restriction sites in the majority of prostate cancers. In order to understand the nature of abnormal methylation of the GSTP1 gene in prostate cancer we undertook a detailed analysis of methylation at 131 CpG sites spanning the promoter and body of the gene. Our results show that DNA methylation is not confined to specific CpG sites in the promoter region of the GSTP1 gene but is extensive throughout the CpG island in prostate cancer cells. Furthermore we found that both alleles are abnormally methylated in this region. In normal prostate tissue, the entire CpG island was unmethylated, but extensive methylation was found outside the island in the body of the gene. Loss of GSTP1 expression correlated with DNA methylation of the CpG island in both prostate cancer cell lines and cancer tissues whereas methylation outside the CpG island in normal prostate tissue appeared to have no effect on gene expression.

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
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8

Similar content being viewed by others

References

  • Batist G, Tulpule A, Sinha B, Katki AG, Meyers CE and Cowan KH. . 1986 J. Biol. Chem. 261: 15544–15549.

  • Baylin SB, Herman JG, Graff JR, Vertino PM and Issa J-P. . (1998). In: Advances in Cancer Research Volume 72. Vandewoude G and Klein G (eds).. Academic Press: San Diego pp. 141–196.

    Google Scholar 

  • Clark S J and Frommer M. . 1995 In: DNA and Nucleoprotein Structure In Vivo. Saluz H and Wiebauer K (eds).. RG Landes Company: Austin, Texas pp. 123–132.

    Google Scholar 

  • Clark SJ, Harrison J and Frommer M. . 1995 Nat. Genet. 10: 20–27.

  • Clark SJ and Frommer, M. . 1997 In: Laboratory Methods for the detection of mutations and polymorphisms in DNA. Taylor G (ed.).. CRC Press: New York pp. 151–162.

    Google Scholar 

  • Clark SJ, Harrison J and Molloy PL. . 1997 Gene 195: 67–71.

  • Clark SJ, Harrison J, Paul, CL and Frommer, M. . 1994 Nucleic Acids Res. 22: 2990–2997.

  • Cookson MS, Reuter VE, Linkov I and Fair WR. . 1997 J. Urol. 157: 673–676.

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

  • Graff JR, Herman JG, Myohanen S, Baylin SB and Vertino PM. . 1997 J. Biol. Chem. 272: 22322–22329.

  • Hayes JD and Pulford DJ. . 1995 Crit. Rev. Biochem. Mol. Biol. 30: 445–600.

  • Isaacs WB, Bova SG, Morton RA, Bussemakers MJG, Brooks JD and Ewing CM. . 1995 Cancer Surveys 23: 19–31.

  • Ishioka C, Kanamaru R, Shibata H, Konishi Y, Ishikawa A, Wakui A, Sato T and Nishihira T. . 1991 Cancer 67: 2560–2564.

  • Jones PA, Rideout WM, Shen J-C, Spruck CH and Tsai C. . 1992 Bioessays 14: 33–36.

  • Knudson JAG. . 1986 Annu. Rev. Genet. 20: 231–251.

  • Laird PW and Jaenisch R. . 1994 Hum. Mol. Genet. 3: 1487–1495.

  • Lengauer C, Kinzler KW and Vogelstein B. . 1997 Proc. Natl. Acad. Sci. USA 94: 2545–2550.

  • Lee WH, Morton RA, Epstein JI, Brooks JD, Campbell PA, Bova GS, Hsieh W-S, Isaacs WB and Nelson WG. . 1994 Proc. Natl. Acad. Sci. USA 91: 11733–11737.

  • Lee PJ, Washer LL, Law DJ, Boland CR, Horon IL and Feinberg AP. . 1996 Proc. Natl. Acad. Sci. USA 93: 10366–10370.

  • Melki JR, Warnecke P, Vincent PC and Clark SJ. . 1998 Leukemia 12: 311–316.

  • Moffat GJ, McLaren AW and Wolf CR. . 1996 J. Biol. Chem. 271: 1054–1060.

  • Morrow CS, Cowan KH and Goldsmith ME. . 1989 Gene 75: 3–11.

  • Moskaluk CA, Duray PH, Cowan KH, Linehan M and Merino MJ. . 1997 Cancer 79: 1595–1599.

  • Mulder TPJ, Verspaget HW, Sier CFM, Roelofs HMJ, Ganesh S, Griffioen G and Peters WHM. . 1995 Cancer Res. 55: 2696–2702.

  • Paul CL and Clark SJ. . 1996 BioTechniques 21: 126–133.

  • Peters WHM, Wornskamp NGM and Theis E. . 1990 Carcinogenesis 11: 1593–1596.

  • Pettaway CA, Pathak S, Greene G, Ramirez E, Wilson MR, Killion JJ and Fidler IJ. . 1996 Clin. Cancer Res. 2: 1627–1636.

  • Rushmore TH and Pickett CB. . 1993 J. Biol. Chem. 268: 11475–11478.

  • Schmutte C, Yang AS, Nguyen TT, Beart RW and Jones PA. . 1996 Cancer Res. 56: 2375–2381.

  • Smith JR, Freije D, Carpten JD, Gronberg H, Xu JF, Isaacs SD, Brownstein MJ, Bova GS, Guo H, Bujnovszky P, Nusskern DR, Damber JE, Bergh A, Emanuelsson M, Kallioniemi OP, Walkerdaniels J, Baileywilson JE, Beaty TH, Meyers DA, Walsh PC, Collins FS, Trent JM and Isaacs WB. . 1996 Science 274: 1371–1374.

  • Stirzaker C, Millar DS, Paul CL, Warnecke PM, Harrison J, Vincent PC, Frommer M and Clark SJ. . 1997 Cancer Res. 57: 2229–2237.

  • Stoger R, Kajimura TM, Brown WT and Laird CD. . 1997 Hum. Mol. Genet. 6: 1791–1801.

  • Tommasi S, LeBon JM, Riggs AD and Singer-Sam J. . 1993 Somat. Cell Mol. Genet. 19: 529–541.

  • Toth M, Müller U and Doerfler W. . 1990 J. Mol. Biol. 214: 673–683.

  • Wang X, Pavelic ZP, Li Y, Gleich L, Gartside PS, Pavelic L, Gluckman JL and Stambrook PL. . 1997 Clin. Cancer Res. 3: 111–114.

  • Warnecke PM, Stirzaker C, Melki JR, Millar DS, Paul CL and Clark SJ. . 1997 Nucl. Acids Res. 25: 4422–4426.

  • Warnecke PM, Biniszkiewicz D, Jaenisch R, Frommer M and Clark SJ. . 1998a Dev.Genet. 22: 111–121.

  • Warnecke PM, Mann J, Frommer M and Clark S. . 1998b Genomics, 51: 182–190.

Download references

Acknowledgements

PC3 cell lines were kindly provided by Dr C Pettaway, MD Anderson Medical Center. We thank Dr P Katelaris, S Danieletto and A Lochhead for support in obtaining prostate tissue samples. This work has been supported by a grant from the NSW Cancer Council. (RG/44/96).

Author information

Authors and Affiliations

  1. Kanematsu Laboratories, Royal Prince Alfred Hospital, Missenden Road, Camperdown, 2050, NSW, Australia

    Douglas S Millar, Cheryl L Paul & Susan J Clark

  2. Oncology Research Centre, Prince of Wales Hospital, Randwick, 2031, NSW, Australia

    Kim K Ow & Pamela J Russell

  3. CSIRO Division of Molecular Science, Sydney Laboratory, PO Box 184, North Ryde, NSW 1670, Australia

    Peter L Molloy & Susan J Clark

Authors
  1. Douglas S Millar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kim K Ow
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Cheryl L Paul
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Pamela J Russell
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Peter L Molloy
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Susan J Clark
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Millar, D., Ow, K., Paul, C. et al. Detailed methylation analysis of the glutathione S-transferase π (GSTP1) gene in prostate cancer. Oncogene 18, 1313–1324 (1999). https://doi.org/10.1038/sj.onc.1202415

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1202415

Keywords

This article is cited by

Search

Advanced search

Quick links