Expression of the pluripotent transcription factor OCT4 promotes cell migration in endometriosis

Expression of the pluripotent transcription factor OCT4 promotes cell migration in endometriosis
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DOI:
10.1016/j.fertnstert.2012.11.033
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发表时间:
2013-04-01
影响因子:
6.7
通讯作者:
Tzeng, Chii-Ruey
Tzeng, Chii-Ruey
中科院分区:
医学2区
文献类型:
--
作者:
Chang, Jui-Hung;Au, Heng-Kien;Tzeng, Chii-Ruey

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目的:为了确定多能转录因子OCT 4在子宫内膜细胞迁移和子宫内膜异位症中的影响。设计:OCT 4表达和细胞迁移研究。设置:研究机构和生殖医学诊所。患者:9名正常子宫内膜受试者,3名正常子宫肌层受试者,36名增生子宫内膜患者和58名子宫内膜异位症患者。干预措施:采用逆转录和实时定量聚合酶链反应(PCR)分析OCT 4 mRNA在正常子宫内膜、正常子宫肌层、增生性子宫内膜和异位子宫内膜组织中的表达。OCT 4表达对子宫内膜细胞迁移活性的影响进行了检测。主要结果测量:逆转录和定量实时PCR,Western印迹,伤口闭合和transwell assays. Results(s):OCT 4和NANOG信使RNA的表达在异位子宫内膜组织中显著高于正常子宫内膜,正常子宫肌层,增生性子宫内膜。OCT 4 mRNA水平与细胞迁移相关基因的表达呈正相关。OCT 4蛋白在原代人子宫内膜间质细胞和人RL 95 -2和HEC 1A子宫内膜癌细胞系中的过表达导致E-CADHERIN水平降低,VIMENTIN、TWIST和SLUG蛋白表达增加,以及在transwell和伤口闭合测定中子宫内膜细胞迁移活性增加。OCT 4基因的转录在人异位增生组织中显著上调。OCT 4的表达可能通过刺激子宫内膜细胞的迁移活动而参与异位子宫内膜生长的病理过程。(Fertil Steril(R)2013; 99:1332-9. (C)美国生殖医学会(American Society for Reproductive Medicine)
Objective: To identify the impact of the pluripotent transcription factor OCT4 in endometrial cell migration and endometriosis.Design: The OCT4 expression and cell migration study.Setting: Research institution and reproductive medical clinic.Patient(s): Nine subjects with normal endometrium, 3 subjects with normal myometrium, 36 patients with hyperplastic endometrium, and 58 patients with endometriosis.Intervention(s): The expression of OCT4 messenger RNA in normal endometrium, normal myometrium, hyperplastic endometrium, and ectopic endometriotic tissues was analyzed using reverse transcription and quantitative real-time polymerase chain reaction (PCR). The effect of OCT4 expression on the migration activity of the endometrial cells was examined.Main Outcome Measure(s): Reverse transcription and quantitative real-time PCR, Western blotting, and wound closure and transwell assays.Result(s): The expression of OCT4 and NANOG messenger RNA was significantly higher in ectopic endometriotic tissues, compared with that of the normal endometrium, the normal myometrium, and the hyperplastic endometrium. The level of OCT4 messenger RNA in endometriotic tissues was positively correlated with the expression of genes associated with cell migration. Overexpression of the OCT4 protein in primary human endometriotic stromal cells and human RL95-2 and HEC1A endometrial carcinoma cell lines resulted in decreased levels of E-CADHERIN, the increased expression of the VIMENTIN, TWIST, and SLUG proteins, and an increase in the migration activity of endometrial cells in transwell and wound closure assays.Conclusion(s): The transcription of the OCT4 gene is significantly up-regulated in human ectopic endometriotic tissues. The expression of OCT4 may contribute to the pathology of ectopic endometrial growth by stimulating the migration activity of endometrial cells. (Fertil Steril (R) 2013; 99: 1332-9. (C) 2013 by American Society for Reproductive Medicine.)