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  • 彭书敏,王凯,詹光熙,等.MTA3通过β-hCG调控上皮性卵巢癌侵袭转移的机制研究[J].同济大学学报(医学版),2017,38(4):1-5, 12.    [点击复制]
  • PENG Shu-min,WANG Kai,ZHAN Guang-xi,et al.Expression of MTA3 in epithelial ovarian cancer and its relation to tumor invasion and metastasis[J].同济大学学报(医学版),2017,38(4):1-5, 12.   [点击复制]
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MTA3通过β-hCG调控上皮性卵巢癌侵袭转移的机制研究
彭书敏,王凯,詹光熙,美丽古丽·莫合买提,郭晓青
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(石河子大学医学院,新疆 石河子 832003;同济大学附属第一妇婴保健院转化医学研究中心,上海 200040;同济大学附属第一妇婴保健院妇科,上海 200040)
摘要:
目的探讨上皮性卵巢癌(epithelial ovarian cancer, EOC)转移相关基因3(metastasis associated gene 3, MTA3)的表达及其与肿瘤 侵袭转移的关系。方法 收集晚期(FIGO Ⅲ-Ⅳ期)EOC术中冰冻标本(8例)及石蜡标本(21例),qRT-PCR和IHC检测卵巢部位肿瘤组织和转移瘤组织中MTA3的表达;Transwell细胞迁移实验观察下调MTA3、下调β-hCG、同时下调MTA3和β-hCG的EOC细胞株(SKOV3和ES-2)体外迁移力的变化。EOC细胞体外分别转染50、100、200nmol/L siRNA-MTA3,qRT-PCR检测分析MTA3和β-hCG的表达相关性;qRT-PCR及Western印迹法检测分析下调MTA3对β-hCG以及上皮间质转化(EMT)标记物E-cadherin、N-cadherin表达的调控作用。结果 qRT-PCR、IHC示EOC转移瘤组织中MTA3的表达显著低于卵巢部位肿瘤组织(P<0.05);Transwell细胞迁移实验示下调MTA3显著增强了EOC细胞的迁移能力(P<0.001),下调β-hCG显著降低了EOC细胞的迁移能力(P<0.001),下调MTA3下调β-hCG显著降低了EOC细胞的迁移能力(P<0.001);qRT-PCR示MTA3与β-hCG的表达呈显著负相关(P<0.05);qRT-PCR、Western印迹法示MTA3下调时,β-hCG和N-cadherin的表达显著上调,而E-cadherin的表达则显著下调。结论 MTA3可能通过β-hCG干预EMT进程,进而调控上皮性卵巢癌侵袭转移。
关键词:  上皮性卵巢癌  MTA3  β-hCG  EMT  肿瘤转移
DOI:10.16118/j.1008-0392.2017.04.001
投稿时间:2017-03-12
基金项目:国家自然科学基金面上项目(81372305)
Expression of MTA3 in epithelial ovarian cancer and its relation to tumor invasion and metastasis
PENG Shu-min,WANG Kai,ZHAN Guang-xi,MEILIGULI MoheMaiti,GUO Xiao-qing
(Medical College, Shihezi University, Shihezi 832003, Xinjiang, China;Clinical and Translational Research Center, First Maternity and Infant Hospital, Tongji University, Shanghai 200040, China;Dept.of Gynaecology, First Maternity and Infant Hospital, Tongji University, Shanghai 200040, China)
Abstract:
Objective To investigate the expression of metastasis associated gene 3 (MTA3) in epithelial ovarian cancer (EOC) and its relation to tumor invasion and metastasis. Methods The frozen tissue (8 cases) and paraffin embedded tissue (21 cases) specimens of advanced EOC (FIGO Ⅲ-Ⅳ) were collected. The expression of MTA3 in ovarian cancers tissues and metastasis tissues were detected by qRT-PCR and immunohistochemical staining (IHC). Human epithelial ovarian carcinoma SKOV3 and ES-2 cells were transfected with siRNA-MTA3, siRNA-β-hCG, both siRNA-MTA3 and siRNA-β-hCG, respectively. The migration of transfected SKOV3 and ES-2 cells was examined by Transwell assay. EOC SKOV3 and ES-2 cells were transfected with 50,0, 200 nmol/L siRNA-MTA3 and qRT-PCR was used to detect the correlation of MTA3 and β-hCG. The mRNA and protein expression of β-hCG, E-cadherin and N-cadherin was detected by qRT-PCR and Western blotting after down-regulated MTA3. Results The expression of MTA3 in metastatic tissue of ovarian cancer was significantly lower than that in primary ovarian tumor (P<0.05). Transwell assay showed that the migration ability of EOC cells was significantly enhanced after down-regulation of MTA3; while it was decreased after down-regulation of β-hCG; when MTA3 and β-hCG were both down-regulated the cell migration ability was markedly decreased (P<0.001). qRT-PCR showed a significant negative correlation between the expression of MTA3 and β-hCG in EOC cell lines (P<0.05). qRT-PCR and Western blotting showed that down-regulation of MTA3 reduced the epithelial markers E-cadherin, while increased the expression of β-hCG and mesenchymal marker N-cadherin. Conclusion MTA3 may up-regulate β-hCG expression to enhance the invasion and metastasis in epithelial ovarian carcinoma through epithelial-mesenchymal transition.
Key words:  epithelial ovarian cancer  MTA3  β-hCG  EMT  tumor metastasis

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