Promoter hypomethylation, especially around the E26 transformation-specific motif, and increased expression of poly (ADP-ribose) polymerase 1 in BRCA-mutated serous ovarian cancer.
Promoter hypomethylation, especially around the E26 transformation-specific motif, and increased expression of poly (ADP-ribose) polymerase 1 in BRCA-mutated serous ovarian cancer.
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DOI：
10.1186/1471-2407-13-90
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发表时间：
2013-02-26
期刊：
影响因子：
3.8
通讯作者：
Yang Q
中科院分区：
文献类型：
--
作者：
Bi FF;Li D;Yang Q
聚（ADP-核糖）聚合酶1（PARP 1）过表达在卵巢癌进展中起关键作用，PARP 1抑制剂治疗BRCA突变卵巢癌的临床开发进展迅速。然而，PARP 1表达的调控机制仍不清楚。由启动子甲基化介导的基因表达的改变越来越被认识到，并经常在卵巢癌中报道。因此，我们研究了PARP 1启动子区域的甲基化状态及其与BRCA突变卵巢癌中PARP 1表达的相关性。BRCA突变的浆液性卵巢癌样本和邻近正常卵巢组织的DNA通过亚硫酸氢盐测序进行分析，使用引物集中在PARP 1启动子区域的CpG岛。PARP 1的表达水平通过免疫组织化学和实时PCR进行评估。与正常组织相比，浆液性卵巢癌组织中PARP 1启动子区域的DNA甲基化水平降低，甲基化强度与PARP 1 mRNA水平呈负相关。更重要的是，E26转化特异性（ETS）定义的CpG位点在卵巢癌样本中甲基化程度显著降低。这些结果表明，低甲基化的启动子区域，特别是周围的ETS基序可能发挥作用的PARP 1表达的上调在卵巢癌的进展。
Poly (ADP-ribose) polymerase 1 (PARP1) overexpression plays a critical role in ovarian cancer progression and the clinical development of PARP1 inhibitors to treat BRCA-mutated ovarian cancer has advanced rapidly. However, the mechanism regulating PARP1 expression remains unknown. Alterations in gene expression mediated by promoter methylation are being increasingly recognized and have frequently been reported in ovarian cancer. We therefore investigated the methylation status of the PARP1 promoter region and its correlation with PARP1 expression in BRCA-mutated ovarian cancer. DNA from BRCA-mutated serous ovarian cancer samples and adjacent normal ovarian tissues were analyzed by bisulfite sequence using primers focusing on the CpG island in the promoter region of PARP1. Expression levels of PARP1 were assessed by immunohistochemistry and real-time PCR. Serous ovarian cancer tissues displayed decreased DNA methylation in the promoter region of PARP1 compared to normal tissue, and methylation intensity correlated inversely with PARP1 mRNA levels. More importantly, E26 transformation-specific (ETS) defined CpG sites were significantly less methylated in ovarian cancer samples. These results indicate that hypomethylation of the promoter region, especially around the ETS motif might play a role in the upregulation of PARP1 expression in the progression of ovarian cancer.
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DOI：
10.1097/01.pgp.0000235064.93182.ec
发表时间：
2007-04-01
影响因子：
2.4
作者：
Brustmann, Hermann
通讯作者：
Brustmann, Hermann
影响因子：
10.3
作者：
Esteller, M;Silva, JM;Herman, JG
通讯作者：
Herman, JG
影响因子：
7.2
作者：
Barnett, Jason C.;Bean, Sarah M.;Berchuck, Andrew
通讯作者：
Berchuck, Andrew
Parp1 位于 Dnmt1 启动子内，并通过其酶活性保护其非甲基化状态。
影响因子：
3.7
作者：
Zampieri, Michele;Passananti, Claudio;Calabrese, Roberta;Perilli, Mariagrazia;Corbi, Nicoletta;De Cave, Fabiana;Guastafierro, Tiziana;Bacalini, Maria Giulia;Reale, Anna;Amicosante, Gianfranco;Calabrese, Lilia;Zlatanova, Jordanka;Caiafa, Paola
通讯作者：
Caiafa, Paola
影响因子：
30.8
作者：
SIMARD, J;TONIN, P;NAROD, SA
通讯作者：
NAROD, SA