Park Jong Y, Zheng Weipeng, Kim Donghwa, Cheng Jin Q, Kumar Nagi, Ahmad Nazeel, Pow-Sang Julio
Division of Cancer Prevention and Control, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA.
Cancer Detect Prev. 2007;31(5):359-65. doi: 10.1016/j.cdp.2007.09.002. Epub 2007 Nov 26.
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.
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.
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%).
These data suggested that DNA methylation in the SLC5A8 promoter region suppressed the expression of SLC5A8 in prostate tumor.
前列腺是男性癌症最常见的发生部位，也是男性癌症死亡的第三大主要原因。溶质载体家族5（碘转运体）成员8（SLC5A8）被认为是一种潜在的肿瘤抑制基因，在各种肿瘤中因表观遗传变化而沉默。本研究旨在探讨DNA甲基化在前列腺肿瘤中SLC5A8表达中的意义。
通过亚硫酸氢盐修饰测序、逆转录聚合酶链反应（RT-PCR）和定量甲基化特异性PCR（QMSP）分析，评估前列腺癌细胞系、同一前列腺癌患者的肿瘤组织及相邻非肿瘤前列腺组织中SLC5A8启动子区域的DNA甲基化状态及其表达情况。
在70%的肿瘤组织中观察到SLC5A8表达降低或缺失。对不表达SLC5A8的前列腺癌细胞系进行亚硫酸氢盐修饰测序分析，检测到SLC5A8启动子区域高度甲基化。用DNA甲基转移酶抑制剂5-氮杂胞苷处理可使SLC5A8重新激活，而曲古抑菌素A（TSA）则不能。与相邻非肿瘤组织相比，原发性前列腺肿瘤组织中SLC5A8启动子区域的甲基化水平更高（7/10，70%）。
这些数据表明，SLC5A8启动子区域的DNA甲基化抑制了前列腺肿瘤中SLC5A8的表达。
