title: Epigenetic silencing of the sulfotransferase 1A1 gene by hypermethylation in breast tissue.
abstract: Sulfotransferase 1A1 (SULT1A1) is reported to be involved in the conjugation with sulfate, resulting in the inactivation of estrogens. Aberrant methylation of promoter CpG islands is known to be responsible for the alteration and silencing of the gene in cancers. This study was intended to evaluate the methylation status and transcriptional activity of SULT1A1 in breast cancer tissue (n=56), benign breast tissue (n=20) and morphologically normal breast tissue (n=20), examined by bisulfite genomic sequencing and reverse transcription (RT)-PCR. As a result, the methylation of the proximal promoter (P1) was identified in 64.3% of breast carcinomas, 15% of normal and 20% of benign breast tissues. In terms of the distal promoter (P0), 32 of 56 cancer tissues (57.1%) were methylated, while 4 normal (20%) and 6 benign tissues (30%) were methylated. Breast cancer tissue showed a higher methylation rate of SULT1A1 than normal and benign tissue at both P1 (p=0.001) and P0 (p=0.006) promoters with statistical significance. Furthermore, cancer tissue showed a higher methylation density rate than normal and benign breast tissue at both P1 and P0 promoters (P1, p=0.001; P0, p=0.001). The tissues that showed aberrant methylation of SULT1A1 did not express mRNA significantly, compared with the unmethylated cases (P1, p=0.003; P0, p=0.023). Although the number of samples was relatively small, our results suggest that DNA methylation in the SULT1A1 gene appears to be present in breast tissue including cancer and methylation significantly impacts transcriptional silencing of the gene. In addition, it can be suggested that progressive SULT1A1 methylation within the promoter area of the gene occurs during breast carcinogenesis.
authors.affiliation: Department of Biology, Dongguk University, Seoul, Korea.
authors.forename: Min Sook
authors.initials: MS
authors.lastname: Kwon
authors.forename: Sun Jung
authors.initials: SJ
authors.lastname: Kim
authors.forename: Su-Young
authors.initials: SY
authors.lastname: Lee
authors.forename: Jeong Hae
authors.initials: JH
authors.lastname: Jeong
authors.forename: Eun Sook
authors.initials: ES
authors.lastname: Lee
authors.forename: Han-Sung
authors.initials: HS
authors.lastname: Kang
mesh_terms: D015239:Arylsulfotransferase / Q000235:genetics*; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D052138:Genes, Neoplasm / Q000235:genetics; D006801:Humans; D011401:Promoter Regions, Genetic
chemical_list: D015239:Arylsulfotransferase; C117544:SULT1A1 protein, human