Hypomethylation of ETS transcription factor binding sites and upregulation of PARP1 expression in endometrial cancer.
Hypomethylation of ETS transcription factor binding sites and upregulation of PARP1 expression in endometrial cancer.
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DOI：
10.1155/2013/946268
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发表时间：
2013
影响因子：
--
通讯作者：
Yang Q
中科院分区：
文献类型：
--
作者：
Bi FF;Li D;Yang Q
尽管PARP1启动子甲基化参与了人角质形成细胞系和淋巴母细胞系中PARP1表达的调节，但其在人子宫内膜癌中的作用尚不清楚。采用针对PARP1核心启动子区的引物，通过亚硫酸氢盐测序分析了40例正常子宫内膜（NE）和50例子宫内膜腺癌（EAC）组织的DNA。PARP 1的表达水平通过免疫组织化学和实时PCR进行评估。患者的临床病理特征和PARP1蛋白水平之间的关联通过Fisher精确检验进行评估。EAC组织中PARP1 mRNA和蛋白表达均高于正常对照组（P < 0.05）。EAC组织中PARP1启动子ETS基序内的CpG基序甲基化程度较低，NE和EAC组织中PARP1 mRNA表达水平与甲基化位点数呈显著负相关（R2 = 0.2 6 2，P <0.0 0 1）。值得注意的是，PARP1蛋白表达与FIGO分期（P = 0.026）、组织学分级（P = 0.002）和体重指数（P = 0.04）相关。我们的研究结果表明，PARP1的过度表达可能参与子宫内膜癌的进展，并在核心启动子区域的ETS基序内的CpG位点的异常低甲基化可能是负责EAC组织中PARP1的过度表达。
Although PARP1 promoter methylation is involved in the regulation of PARP1 expression in human keratinocyte lines and lymphoblastoid cell lines, its roles in human endometrial cancer are unknown. DNA from forty normal endometrium (NE) and fifty endometrial adenocarcinoma (EAC) tissues were analyzed by bisulfite sequencing using primers focusing on the core promoter region of PARP1. Expression levels of PARP1 were assessed by immunohistochemistry and real-time PCR. Associations between patient clinicopathological characteristics and PARP1 protein levels were assessed by Fisher's exact test. Here, PARP1 mRNA and protein were overexpressed in EAC tissues (P < 0.05). CpG sites within the ETS motif in the PARP1 promoter exhibited significant hypomethylation in EAC tissues, and there was a significant negative correlation between PARP1 mRNA levels and the number of methylated sites in both NE and EAC tissues (R 2 = 0.262, P < 0.001). Notably, PARP1 protein expression was associated with FIGO stage (P = 0.026), histological grade (P = 0.002) , and body mass index (P = 0.04). Our findings imply that PARP1 overexpression may participate in endometrial cancer progression, and abnormal hypomethylation of CpG sites within the ETS motif in the core promoter region may be responsible for PARP1 overexpression in EAC tissues.
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影响因子：
7.2
作者：
Sorosky, Joel I.
通讯作者：
Sorosky, Joel I.
基因组和生化洞察ETS转录因子的特异性。
影响因子：
16.6
作者：
Hollenhorst PC;McIntosh LP;Graves BJ
通讯作者：
Graves BJ
影响因子：
8
作者：
Soldatenkov, VA;Albor, A;Notario, V
通讯作者：
Notario, V
影响因子：
7
作者：
Varley KE;Gertz J;Bowling KM;Parker SL;Reddy TE;Pauli-Behn F;Cross MK;Williams BA;Stamatoyannopoulos JA;Crawford GE;Absher DM;Wold BJ;Myers RM
通讯作者：
Myers RM
影响因子：
29
作者：
Bai P;Cantó C;Oudart H;Brunyánszki A;Cen Y;Thomas C;Yamamoto H;Huber A;Kiss B;Houtkooper RH;Schoonjans K;Schreiber V;Sauve AA;Menissier-de Murcia J;Auwerx J
通讯作者：
Auwerx J