Candidate tumor suppressor gene SLC5A8 is frequently down-regulated by promoter hypermethylation in prostate tumor
Candidate tumor suppressor gene SLC5A8 is frequently down-regulated by promoter hypermethylation in prostate tumor
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DOI：
10.1016/j.cdp.2007.09.002
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发表时间：
2007-01-01
影响因子：
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通讯作者：
Pow-Sang, Julio
中科院分区：
文献类型：
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作者：
Park, Jong Y.;Zheng, Weipeng;Pow-Sang, Julio
背景：前列腺是最常见的癌症部位，也是男性癌症死亡的第三大原因。溶质载体家族5（碘转运蛋白）成员8（SLC 5A 8）被认为是一个潜在的肿瘤抑制基因，在各种肿瘤中被表观遗传学改变沉默。本研究的目的是探讨DNA甲基化在前列腺肿瘤中SLC 5A 8表达的意义。研究方法：采用亚硫酸氢盐修饰测序、RT-PCR和定量甲基化特异性PCR（QMSP）分析方法，检测前列腺癌细胞系、前列腺癌患者肿瘤组织和癌旁非肿瘤组织中SLC 5A 8基因启动子区DNA甲基化状态和表达。结果：70%的肿瘤组织中SLC 5A 8表达减少或缺失。对不表达SLC 5A 8的前列腺癌细胞系的亚硫酸氢盐修饰的测序分析检测到密集甲基化的SLC 5A 8启动子区域。用DNA甲基转移酶抑制剂5-氮杂胞苷处理可使SLC 5A 8重新活化，但不能用阿司他丁A（TSA）。在原发性前列腺肿瘤组织中检测到的SLC 5A 8启动子区域的甲基化程度高于邻近非肿瘤组织（7/10，70%）。结论：前列腺肿瘤中SLC 5A 8基因启动子区甲基化抑制了SLC 5A 8的表达。(c)2007年国际预防肿瘤学会。由爱思唯尔有限公司出版。保留所有权利。
Background: The prostate gland is the most common site of cancer and the third leading cause of cancer mortality in men. Solute carrier family 5 (iodide transporter), member 8 (SLC5A8) was proposed as a potential tumor suppressor gene which is silenced by epigenetic changes in various tumors. The aim of this study was to investigate the significance of DNA methylation in SLC5A8 expression in prostate tumors. Methods: DNA methylation status of the promoter region and expression of SLC5A8 were evaluated in prostate cancer cell lines, tumor and adjacent non-tumor prostate tissues from same prostate cancer patients, by using bisulphite-modified sequencing, RT-PCR and quantitative methylation-specific PCR (QMSP) analysis. Results: The reduced or lost expression of SLC5A8 was observed in 70% of the tumor tissues. The bisulphite-modified sequencing analysis on the prostate cancer cell lines which do not express SLC5A8 detected the densely methylated SLC5A8 promoter region. SLC5A8 was reactivated by treatment with DNA methyl transferase inhibitor, 5-azacytidine but not by trichostatin A (TSA). Higher methylation at the promoter region of SLC5A8 in primary prostate tumor tissues was detected as compared with those in adjacent non-tumor tissues (7/10, 70%). Conclusions: These data suggested that DNA methylation in the SLC5A8 promoter region suppressed the expression of SLC5A8 in prostate tumor. (c) 2007 International Society for Preventive Oncology. Published by Elsevier Ltd. All rights reserved.