GSTP1 CpG island DNA hypermethylation in hepatocellular carcinomas.

  • Authors:
    • J C Tchou
    • X Lin
    • D Freije
    • W B Isaacs
    • J D Brooks
    • A Rashid
    • A M De Marzo
    • Y Kanai
    • S Hirohashi
    • W G Nelson
  • View Affiliations

  • Published online on: Saturday, April 1, 2000
  • Pages: 663-739
  • DOI: 10.3892/ijo.16.4.663

Abstract

Glutathione S-transferases, enzymes that defend cells against damage mediated by oxidant and electrophilic carcinogens, may be critical determinants of cancer pathogenesis. We report here that the pathogenesis of hepatocellular carcinoma (HCC), one of the most common cancers in the world, frequently involves an accumulation of somatic <CpG island> DNA methylation changes at GSTP1, the gene encoding the pi-class glutathione S-transferase. For our study, Hep3B HCC cells and a cohort of 20 HCC tissue specimens were subjected to analysis for GSTP1 expression and for somatic GSTP1 alterations. GSTP1 <CpG island> DNA hypermethylation in HCC DNA was assessed by Southern blot analysis, via a polymerase chain reaction (PCR) assay, and by using a genomic sequencing approach. Hep3B HCC cells failed to express GSTP1 mRNA or GSTP1 polypeptides. Similarly, HCC cells in 19 of 20 HCC cases were devoid of GSTP1 polypeptides. By Southern blot analysis, DNA from Hep3B HCC cells displayed abnormal GSTP1 <CpG island> hypermethylation. Treatment of Hep3B HCC cells in vitro with the DNA methyltransferase inhibitor 5-aza-deoxycytidine both reversed GSTP1 <CpG island> DNA hypermethylation and restored GSTP1 expression. Using a PCR assay, somatic GSTP1 <CpG island> DNA hypermethylation was also detected in HCC DNA from 17 of 20 HCC cases. Genomic sequencing analyses, undertaken to map 5-methyldeoxycytidine nucleotides located at the GSTP1 transcriptional regulatory region, frequently detected somatic DNA hypermethylation near the gene promoter in HCC DNA. The data indicate that GSTP1 <CpG island> DNA hypermethylation changes appear frequently in human HCC. In addition, the data raise the possibility that somatic GSTP1 inactivation, via <CpG island> hypermethylation, may contribute to the pathogenesis of HCC.
Journal Cover

April 2000
Volume 16 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

2013 Impact Factor: 2.773
Ranked #30/202 Oncology
(total number of cites)

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APA
Tchou, J., Lin, X., Freije, D., Isaacs, W., Brooks, J., Rashid, A., De Marzo, A., Kanai, Y., Hirohashi, S., & Nelson, W. (2000). GSTP1 CpG island DNA hypermethylation in hepatocellular carcinomas.. International Journal of Oncology, 16(4), 663-739.
MLA
Tchou, Lin, Freije, Isaacs, Brooks, Rashid, De Marzo, Kanai, Hirohashi, and W G Nelson. "GSTP1 CpG island DNA hypermethylation in hepatocellular carcinomas.." International Journal of Oncology International Journal of Oncology 16.4 (2000): 663-739.
Chicago
Tchou, Lin, Freije, Isaacs, Brooks, Rashid, De Marzo, Kanai, Hirohashi, and W G Nelson. "GSTP1 CpG island DNA hypermethylation in hepatocellular carcinomas.." International Journal of Oncology International Journal of Oncology 16 no. 4 (2000): 663-739.