Kwon 13_5
نویسندگان
چکیده
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. Introduction Carcinogen-metabolizing enzymes are involved in the activation and deactivation of a diverse group of chemical carcinogens (1,2). Sulfation is generally considered to be a high-affinity metabolic reaction (i.e., likely to be important in low exposure situations), which can result in either bioinactivation or detoxification of xenobiotics as well as important endogenous chemicals such as iodothyronines, catecholamines and estrogens (3). Conjugation with sulfate gives rise to the inactivation of estrogens because the addition of the charged sulfonate group averts the binding of the steroid to its receptor, thereby terminating its mitogenic effects. Sulfation reactions are catalyzed by the gene products of the cytosolic sulfotransferase (SULT) gene superfamily, which in humans comprises of at least 10 genes falling into three subfamilies (4,5). To date, at least seven characterized isoforms are known to make up the human phenol SULT family (6). In adult human tissue, the product of the SULT1A1 gene is the major form of phenol SULT. SULT1A1 protein is found almost ubiquitously in human tissues and is known to metabolize hydroxylated aryl amines (7) and heterocyclic amines (8). The SULT1A1 gene has two specific promoters, distal (P0) and proximal (P1), which induce cDNAs heterogeneous in the 5'-untranslated region (UTR). Tissue specific promoter usage has been suggested for the separated cis-acting promoter sequences (9,10). There is promising evidence that the de novo methylation of promoter cytosine guanine dinucleotide (CpG) islands, contributes to the alteration of transcriptional expression in cancer and is associated with gene silencing (11). To the best of our knowledge, no reports have been published with reference to the methylation of the SULT1A1 gene in bona fide human tissue. Therefore, we assessed the methylation status of both proximal (P1) and distal promoters (P0) of the SULT1A1 gene in normal, benign and cancer tissues of the breast. We also evaluated the mRNA expression of the SULT1A1 gene in breast tissue with or without methylation of the gene. Materials and methods Tissue samples and nucleic acid extraction. Formalin-fixed and paraffin-embedded specimens were obtained from the ONCOLOGY REPORTS 15: 27-32, 2006 27 Epigenetic silencing of the sulfotransferase 1A1 gene by hypermethylation in breast tissue MIN SOOK KWON1, SUN JUNG KIM1, SU-YOUNG LEE2, JEONG HAE JEONG2, EUN SOOK LEE2 and HAN-SUNG KANG2 1Department of Biology, Dongguk University, Seoul 100-715; 2Research Institute and Hospital, National Cancer Center, Gyeonggi do 411-764, Korea Received May 13, 2005; Accepted July 6, 2005 _________________________________________ Correspondence to: Dr Han-Sung Kang, Center for Breast Cancer, National Cancer Center, Gyeonggi do 411-764, Korea E-mail: [email protected] Abbreviations: CpG, cytosine guanine dinucleotide; SULT, sulfotransferase; RT, reverse transcriptase; PCR, polymerase chain reaction
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متن کاملAuthor's response to reviews Title: Clinical significance of preoperative serum vascular endothelial growth factor, interleukin-6, and C-reactive protein level in colorectal cancer. Authors:
Kyung A Kwon ([email protected]) Sung Hyun Kim ([email protected]) Sung Yong Oh ([email protected]) Suee Lee ([email protected]) Jin-Yeong Han ([email protected]) Kyeong Hee Kim ([email protected]) Ri Young Goh ([email protected]) Hong Jo Choi ([email protected]) Ki Jae Park ([email protected]) Mee Sook Roh ([email protected]) Hyo-Jin Kim ([email protected]) Hyuk-Chan Kwon ([email protected]) Jong H...
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