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

Huang, Y; He, T; Domann, F E

Huang, Y; He, T; Domann, F E.

Afiliación

Huang Y; Department of Radiology, College of Medicine, University of Iowa, Iowa City 52242, USA.

DNA Cell Biol ; 18(8): 643-52, 1999 Aug.

Article en En | MEDLINE | ID: mdl-10463060

RESUMEN

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.

Asunto(s)

Citosina/metabolismo; Metilación de ADN; Regulación hacia Abajo; Regulación Enzimológica de la Expresión Génica; Regulación Neoplásica de la Expresión Génica; Superóxido Dismutasa/genética; Elementos Alu/genética; Línea Celular Transformada; Transformación Celular Neoplásica/genética; Islas de CpG/genética; Fibroblastos/metabolismo; Genes Supresores de Tumor/genética; Humanos; Intrones/genética; Pulmón; Modelos Genéticos; Polimorfismo Genético/genética; ARN Mensajero/genética; ARN Mensajero/metabolismo; Virus 40 de los Simios; Superóxido Dismutasa/metabolismo

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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Superóxido Dismutasa / Regulación hacia Abajo / Regulación Enzimológica de la Expresión Génica / Regulación Neoplásica de la Expresión Génica / Metilación de ADN / Citosina Tipo de estudio: Risk_factors_studies Límite: Humans Idioma: En Revista: DNA Cell Biol Asunto de la revista: BIOLOGIA MOLECULAR Año: 1999 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos

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