TGFBI promoter hypermethylation correlating with paclitaxel chemoresistance in ovarian cancer.
TGFBI promoter hypermethylation correlating with paclitaxel chemoresistance in ovarian cancer.
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TGFBI启动子高甲基化与卵巢癌紫杉醇化疗耐药相关
DOI：
10.1186/1756-9966-31-6
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发表时间：
2012-01-16
期刊：
影响因子：
--
通讯作者：
Yang X
中科院分区：
文献类型：
--
作者：
Wang N;Zhang H;Yao Q;Wang Y;Dai S;Yang X
本研究旨在探讨卵巢癌组织中转化生长因子β诱导基因h3的甲基化状态及其与紫杉醇耐药的关系。采用甲基化特异性聚合酶链式反应(MSP)和亚硫酸氢盐测序聚合酶链式反应(BSP)检测卵巢癌和正常卵巢组织中TGFBI基因的甲基化状态。采用实时定量聚合酶链式反应、Western blotting和四甲基偶氮唑盐比色法比较去甲基化药物5-氮-2‘-脱氧胞苷(5-aza-2’-deoxcytidine，5-aza-DC)作用于SKOV3、SKOV3/tr、SKOV3/DDP、A2780、2780/tr、OVCAR8等6种细胞株前后TGFBI的表达和细胞活力。在我们的结果中，29/40(72.5%)的卵巢癌和1/10(10%)的卵巢良性肿瘤中检测到TGFBI甲基化。正常卵巢组织中未检测到甲基化(P<；0.001)。未观察到RUNX3甲基化与临床病理特征的统计学相关性。TGFBI甲基化与TGFBI基因表达缺失显著相关(P<；0.001)。紫杉醇耐药细胞株(SKOV3/tr和2780/tr)TGFBI基因甲基化水平显著高于敏感细胞对(P<；0.001)。经5-aza-DC处理后，SKOV3/tr和A2780/tr细胞中TGFBI基因和蛋白的相对表达显著增加。而在其他细胞中，TGFBI的相对表达和蛋白表达差异无统计学意义(均P>；0.05)，表明TGFBI的重新表达可以逆转紫杉醇的化疗耐药。我们的结果表明，TGFBI在卵巢癌中经常甲基化，并与紫杉醇耐药有关。TGFBI有可能成为提高卵巢癌患者化疗反应的潜在治疗靶点。
The purpose of this study is to determine the methylation status of Transforming growth factor-beta-inducible gene-h3 (TGFBI) and its correlation with paclitaxel chemoresistance in ovarian cancer. The methylation status of TGFBI was examined in ovarian cancer and control groups by methylation-specific PCR (MSP) and bisulfite sequencing PCR (BSP). The TGFBI expression and cell viability were compared by Quantitative Real-Time PCR, Western Blotting and MTT assay before and after demethylating agent 5-aza-2'-deoxycytidine (5-aza-dc) treatment in 6 cell lines (SKOV3, SKOV3/TR, SKOV3/DDP, A2780, 2780/TR, OVCAR8). In our results, TGFBI methylation was detected in 29/40 (72.5%) of ovarian cancer and 1/10 (10%) of benign ovarian tumors. No methylation was detected in normal ovarian tissues (P< 0.001). No statistical correlation between RUNX3 methylation and clinicopathological characteristics was observed. A significant correlation between TGFBI methylation and loss of TGFBI mRNA expression was found (P< 0.001). The methylation level of TGFBI was significantly higher in paclitaxel resistant cell lines (SKOV3/TR and 2780/TR) than that in the sensitive pairs (P< 0.001). After 5-aza-dc treatment, the relative expression of TGFBI mRNA and protein increased significantly in SKOV3/TR and A2780/TR cells. However, no statistical differences of relative TGFBI mRNA expression and protein were found in other cells (allP> 0.05), which showed that re-expression of TGFBI could reverse paclitaxel chemoresistance. Our results show that TGFBI is frequently methylated and associated with paclitaxel-resistance in ovarian cancer. TGFBI might be a potential therapeutic target for the enhancement of responses to chemotherapy in ovarian cancer patients.
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影响因子：
50.3
作者：
Olopade, OI;Wei, MJ
通讯作者：
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影响因子：
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作者：
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Nephew KP
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64.5
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8
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Zhao, YL;Piao, CQ;Hei, TK
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Hei, TK
影响因子：
50.3
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通讯作者：
Brenton JD