Serrano Alfonso, Redondo Maximino, Tellez Teresa, Castro-Vega Isabel, Roldan M Jose, Mendez Rosa, Rueda Antonio, Jimenez Eugenio
Department of Immunology, Hospital Clinico Universitario, Campus Universitario Teatinos, Málaga, Spain.
Tumour Biol. 2009;30(5-6):286-91. doi: 10.1159/000259912. Epub 2009 Nov 20.
BACKGROUND/AIMS: Clusterin has attracted much recent attention because of its association with tumorigenesis and the progression of human carcinomas. The present study was designed to examine the role of clusterin methylation as an indicator of clusterin expression in tumor cell lines and breast tissue samples.
For this purpose, we used methylation-sensitive restriction analysis followed by PCR.
None of the non-tumoral breast samples showed expression of clusterin by immunohistochemistry, and a methylated state was found in the promoter region of the gene. However, a demethylated state was found in 5 of 6 analyzed carcinoma cell lines. Four of 5 demethylated cell lines presented moderate to strong expression of clusterin, while no expression was detected in the unmethylated cell line. The inverse correlation found in most cell lines between clusterin expression and promoter methylation was also found in most human tumors analyzed (p < 0.001). Thus, a methylated state was present in 14 carcinomas, 12 of them with a null expression of clusterin, while a demethylated state was detected in 7 breast tumor samples, with 5 of them presenting strong expression.
We conclude that clusterin expression is under epigenetic control via methylation of its promoter.
背景/目的：近年来，簇集素因其与肿瘤发生及人类癌症进展的关联而备受关注。本研究旨在探讨簇集素甲基化作为肿瘤细胞系和乳腺组织样本中簇集素表达指标的作用。
为此，我们采用甲基化敏感限制性分析及随后的聚合酶链反应。
免疫组织化学检测显示，所有非肿瘤性乳腺样本均未表达簇集素，且在该基因的启动子区域发现甲基化状态。然而，在6个分析的癌细胞系中，有5个呈现去甲基化状态。5个去甲基化细胞系中有4个呈现中度至强的簇集素表达，而未甲基化的细胞系未检测到表达。在大多数分析的人类肿瘤中也发现了大多数细胞系中簇集素表达与启动子甲基化之间的负相关（p < 0.001）。因此，14例癌组织中存在甲基化状态，其中12例簇集素表达缺失，而在7例乳腺肿瘤样本中检测到去甲基化状态，其中5例呈现强表达。
我们得出结论，簇集素的表达受其启动子甲基化的表观遗传控制。
