Genetic and epigenetic alterations of steroidogenic factor‑1 in ovarian tumors.
Genetic and epigenetic alterations of steroidogenic factor‑1 in ovarian tumors.
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DOI：
10.3892/ijo.2012.1758
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发表时间：
2013-02
影响因子：
5.2
通讯作者：
Makridakis NM
中科院分区：
文献类型：
--
作者：
Miller S;Bhasin N;Urrego H;Moroz K;Rowan BG;Ramayya MS;Makridakis NM
类固醇生成因子-1 (SF-1) 是 NR5A1 基因的产物，是一种重要的转录因子，已知可调节卵巢上皮的类固醇生成，包括卵巢癌抑制剂黄体酮的合成。 SF-1 蛋白是一种潜在的卵巢肿瘤抑制因子，已在正常 OSE 细胞中得到证实，但在大多数卵巢肿瘤和卵巢肿瘤细胞系中缺失。我们检查了杂合性丢失 (LOH) 和启动子甲基化作为可能解释卵巢肿瘤组织中 SF-1 蛋白丢失的潜在机制。对匹配的肿瘤/正常组织中的三个 NR5A1 SNP 进行基因分型，成功分析了 16/36 (44%) 的卵巢肿瘤中的 LOH，以及 10% 的肿瘤中的体细胞突变（获得等位基因）。此外，使用甲基化敏感的限制性酶方法证明卵巢肿瘤中 NR5A1 基因甲基化频率（36/46；78%）与正常卵巢（1/11；9%）相比有统计学显着性（p<0.0001）增加。这些数据表明，SF-1 编码基因在卵巢肿瘤中表现出频繁的遗传（LOH/碱基替换）和表观遗传（甲基化）体细胞改变。这些数据还提出了新的分子机制，可以解释卵巢肿瘤中 SF-1 蛋白的丢失及其在卵巢癌发生中的潜在作用。
Steroidogenic factor-1 (SF-1), the product of the NR5A1 gene, is an essential transcription factor that is known to regulate steroidogenesis in ovarian epithelia, including the synthesis of progesterone, a suppressor of ovarian cancer. Expression of the SF-1 protein, a potential ovarian tumor suppressor, has been demonstrated in normal OSE cells, but is lost in most ovarian tumors and ovarian tumor cell lines. We examined loss of heterozygosity (LOH) and promoter methylation as potential mechanisms that may explain the loss of SF-1 protein in ovarian tumor tissues. Genotyping of three NR5A1 SNPs in matched tumor/normal tissues identified LOH in 16/36 (44%) of the ovarian tumors successfully analyzed, and somatic mutations (gain of allele) in 10% of the tumors. Furthermore, a methylation-sensitive restriction enzyme method was used to demonstrate statistically significant (p<0.0001) increase in the frequency of NR5A1 gene methylation in ovarian tumors (36/46; 78%) versus normal ovaries (1/11; 9%). These data suggest that the SF-1 encoding gene exhibits frequent genetic (LOH/base substitution) and epigenetic (methylation) somatic alterations in ovarian tumors. These data also present novel molecular mechanisms that may explain the loss of SF-1 protein in ovarian tumors, and its potential role in ovarian carcinogenesis.
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影响因子：
5.7
作者：
Abd-Elaziz, M;Moriya, T;Sasano, H
通讯作者：
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Bulun, Serdar E.
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Strauss, JF
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Sugawara, T;Kiriakidou, M;Strauss, JF
通讯作者：
Strauss, JF