Methylation-associated silencing of the Wnt antagonist SFRP1 gene in human ovarian cancers
Methylation-associated silencing of the Wnt antagonist SFRP1 gene in human ovarian cancers
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DOI：
10.1111/j.1349-7006.2004.tb03255.x
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发表时间：
2004-09-01
期刊：
影响因子：
5.7
通讯作者：
Ushijima, T
中科院分区：
文献类型：
--
作者：
Takada, T;Yagi, Y;Ushijima, T
SFRP 1基因位于染色体8p11.2，编码Wnt信号拮抗剂，最近被证明是一种新的肿瘤抑制基因，在人类结肠癌中可通过启动子甲基化而失活。在这里，我们分析了SFRP 1基因的启动子甲基化在人类卵巢癌，其中8 p的杂合性丢失是经常观察到的，并参与Wnt信号通路已被建议。甲基化特异性PCR（MSP）分析显示，13个卵巢癌细胞系中的4个和17个原发性卵巢癌中的2个具有甲基化SFRP 1，而永生化卵巢上皮细胞系HOSE和7个卵巢子宫内膜囊肿样本没有。在四个卵巢癌细胞系与甲基化，SFRP 1不表达在所有通过定量RT-PCR分析确定。用去甲基化剂5-氮杂-2 '-脱氧胞苷处理SFRP 1甲基化的细胞系MCAS，观察启动子的去甲基化和SFRP 1的重新表达。这些结果表明，SFRP 1在人类卵巢癌以及结肠癌中通过启动子甲基化而失活。
The SFRP1 gene on chromosome 8p11.2 encodes a Wnt signaling antagonist, and was recently demonstrated to be a new tumor suppressor that is inactivated by promoter methylation in human colon cancers. Here, we analyzed promoter methylation of the SFRP1 gene in human ovarian cancers, in which loss of heterozygosity in 8p is frequently observed and involvement of the Wnt signaling pathway has been suggested. Methylation-specific PCR (MSP) analysis showed that four of 13 ovarian cancer cell lines and two of 17 primary ovarian cancers had methylated SFRP1, while an immortalized ovarian epithelial cell line, HOSE, and seven ovarian endometrial cyst samples did not. In the four ovarian cancer cell lines with the methylation, SFRP1 was not expressed at all as determined by quantitative RT-PCR analysis. A cell line with SFRP1 methylation, MCAS, was treated with a demethylating agent, 5-aza-2'-deoxycytidine, and demethylation of the promoter and re-expression of SFRP1 were observed. These results show that SFRP1 is inactivated by promoter methylation in human ovarian cancers, as well as colon cancers.