Detailed methylation analysis of the glutathione S-transferase π (GSTP1) gene in prostate cancer
Detailed methylation analysis of the glutathione S-transferase π (GSTP1) gene in prostate cancer
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DOI：
10.1038/sj.onc.1202415
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发表时间：
1999-02-11
期刊：
影响因子：
8
通讯作者：
Clark, SJ
中科院分区：
文献类型：
--
作者：
Millar, DS;Ow, KK;Clark, SJ
谷胱甘肽-S-转移酶（GST）是一类保护哺乳动物细胞免受致癌物质和活性氧亲电代谢物侵害的同工酶。以往的研究表明，在大多数前列腺癌中，pi类基因GSTP 1的富含CpG的启动子区域在单个限制性位点甲基化。为了了解前列腺癌中GSTP 1基因异常甲基化的性质，我们对跨越该基因启动子和主体的131个CpG位点的甲基化进行了详细分析。我们的研究结果表明，DNA甲基化并不局限于特定的CpG位点的启动子区的GSTP 1基因，但广泛的整个CpG岛在前列腺癌细胞。此外，我们发现，这两个等位基因在这一地区异常甲基化。在正常的前列腺组织中，整个CpG岛是未甲基化的，但在岛外的基因体中发现了广泛的甲基化。GSTP 1表达的缺失与前列腺癌细胞系和癌组织中CpG岛的DNA甲基化相关，而正常前列腺组织中CpG岛外的甲基化似乎对基因表达没有影响。
Glutathione-S-Transferases (GSTs) comprise a family of isoenzymes that provide protection to mammalian cells against electrophilic metabolites of carcinogens and reactive oxygen species. Previous studies have shown that the CpG-rich promoter region of the pi-class gene GSTP1 is methylated at single restriction sites in the majority of prostate cancers, In order to understand the nature of abnormal methylation of the GSTP1 gene in prostate cancer we undertook a detailed analysis of methylation at 131 CpG sites spanning the promoter and body of the gene. Our results show that DNA methylation is not confined to specific CpG sites in the promoter region of the GSTP1 gene but is extensive throughout the CpG island in prostate cancer cells. Furthermore we found that both alleles are abnormally methylated in this region. In normal prostate tissue, the entire CpG island was unmethylated, but extensive methylation was found outside the island in the body of the gene. Loss of GSTP1 expression correlated with DNA methylation of the CpG island in both prostate cancer cell lines and cancer tissues whereas methylation outside the CpG island in normal prostate tissue appeared to have no effect on gene expression.