Decreased expression of manganese superoxide dismutase in transformed cells is associated with increased cytosine methylation of the SOD2 gene

Yuanhui Huang, Tongrong He, Frederick E. Domann

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Tumor cells express lower levels of manganese superoxide dismutase (MnSOD) than their normal counterparts. Enforced expression of MnSOD reverses the malignant phenotype of many transformed cells, suggesting that SOD2 is a tumor suppressor. The SOD2 gene contains a large CpG island spanning >3.5 kb that starts near the 5' edge of the promoter and extends into intron 2. We hypothesized that the difference in SOD2 expression between tumor cells and their normal cell counterparts might be secondary to differences in their cytosine methylation patterns in this CpG island. To test this hypothesis, we analyzed the methylation status of the SOD2 gene in two cell line models that show differential MnSOD expression between normal and SV40-transformed cells: WI38 and MRC5 and their SV40-transformed variants, WI38-VA and MRC5-VA. We subdivided the SOD2 gene CpG island into 10 individual regions for analysis by bisulfite genomic sequencing. A region located in intron 2 displayed a significant increase in cytosine methylation in both transformed cell lines that expressed low levels of MnSOD mRNA compared with their normal cell counterparts. Recent studies by others have shown that SOD2 intron 2 is a potent transcriptional enhancer. The association between increased cytosine methylation of the SOD2 intron 2 region and decreased MnSOD expression in transformed cells compared with their normal counterparts suggests that an epigenetic mechanism contributes to the differential SOD2 gene expression between these normal and SV40-transformed cells.

Original languageEnglish (US)
Pages (from-to)643-652
Number of pages10
JournalDNA and Cell Biology
Volume18
Issue number8
DOIs
StatePublished - Aug 1999
Externally publishedYes

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Cytosine
Methylation
Superoxide Dismutase
Introns
CpG Islands
Genes
Neoplasms
Transformed Cell Line
Epigenomics
Phenotype
Gene Expression
Cell Line
Messenger RNA

ASJC Scopus subject areas

  • Cell Biology
  • Genetics
  • Molecular Biology

Cite this

Decreased expression of manganese superoxide dismutase in transformed cells is associated with increased cytosine methylation of the SOD2 gene. / Huang, Yuanhui; He, Tongrong; Domann, Frederick E.

In: DNA and Cell Biology, Vol. 18, No. 8, 08.1999, p. 643-652.

Research output: Contribution to journalArticle

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