目的探讨膀胱移行细胞癌组织中A激酶锚定蛋白12（A-kinase anchoring protein 12，AKAPl2）基因mRNA表达水平和基因启动子区CpG岛甲基化程度及其与临床病理参数之间的关系。方法用荧光定量逆转录PCR（FQ-RT-PCR）和甲基化特异性PCR（MS...目的探讨膀胱移行细胞癌组织中A激酶锚定蛋白12（A-kinase anchoring protein 12，AKAPl2）基因mRNA表达水平和基因启动子区CpG岛甲基化程度及其与临床病理参数之间的关系。方法用荧光定量逆转录PCR（FQ-RT-PCR）和甲基化特异性PCR（MSP）检测30份膀胱移行细胞癌组织及其癌旁组织中AKAPl2基因mRNA的表达水平及其启动子区CpG岛甲基化状态。并用亚硫酸盐修饰后PCR产物进行克隆测序。结果在30份膀胱移行细胞癌患者组织标本中，AKAPl2在癌组织中表达下调比率为73．3％（22／30），在病理Ⅱ和Ⅲ级膀胱移行细胞癌中下调比率明显高于Ⅰ级（P=0．02）。MSP检测结果显示，膀胱移行细胞癌甲基化比率为53．3％（16／30），且与膀胱移行细胞癌TNM分期（r=0．52，Prs=0．03）和病理分级（r=0．61，Prs=0．01）有明显的相关性。结论AKAPl2基因启动子区出现的异常甲基化可导致其在膀胱移行细胞癌中的表达沉默，且与膀胱移行细胞癌的发生有关。展开更多
Transcription factors, which represent an important class of proteins that play key roles in controlling cellular proliferation and cell cycle modulation, are attractive targets for cancer therapy. Previous researches...Transcription factors, which represent an important class of proteins that play key roles in controlling cellular proliferation and cell cycle modulation, are attractive targets for cancer therapy. Previous researches have shown that the expression level of activating transcription factor 5 （ATF5） was frequently increased in glioma and its acetylation level was related to glioma. The purposes of this study were to explore the methylation level of ATF5 in clinical glioma tissues and to explore the effect of ATF5 methylation on the expression of ATF5 in glioma. Methylation of the promoter region of ATF5 was assayed by bisulflte-specific polymerase chain reaction （PCR） sequencing analysis in 35 cases of glioma and 5 normal tissues. Quantitative real-time PCR （qRT-PCR） was also performed to detect ATF5 mRNA expression in 35 cases of glioma and 5 normal tissues. Clinical data were collected from the patients and analyzed. The percentages of methylation of the ATF5 gene in the promoter region in healthy control, patients with well-differentiated glioma, and those with poorly differentiated glioma were 87.78%, 73.89%, and 47.70%, respectively. Analysis of the methylation status of the promoter region of the ATF5 gene showed a gradually de- creased methylation level in poorly differentiated glioma, well-differentiated glioma, and normal tissues （P〈0.05）. There was also a significant difference between well-differentiated glioma and poorly differentiated glioma （P〈0.05）. ATF5 mRNA expression in glioma was significantly higher than that in the normal tissues （P〈0.05）. This study provides the first evidence that the methylation level of ATF5 decreased, and its mRNA expression was evidently up-regulated in glioma.展开更多
文摘目的探讨膀胱移行细胞癌组织中A激酶锚定蛋白12（A-kinase anchoring protein 12，AKAPl2）基因mRNA表达水平和基因启动子区CpG岛甲基化程度及其与临床病理参数之间的关系。方法用荧光定量逆转录PCR（FQ-RT-PCR）和甲基化特异性PCR（MSP）检测30份膀胱移行细胞癌组织及其癌旁组织中AKAPl2基因mRNA的表达水平及其启动子区CpG岛甲基化状态。并用亚硫酸盐修饰后PCR产物进行克隆测序。结果在30份膀胱移行细胞癌患者组织标本中，AKAPl2在癌组织中表达下调比率为73．3％（22／30），在病理Ⅱ和Ⅲ级膀胱移行细胞癌中下调比率明显高于Ⅰ级（P=0．02）。MSP检测结果显示，膀胱移行细胞癌甲基化比率为53．3％（16／30），且与膀胱移行细胞癌TNM分期（r=0．52，Prs=0．03）和病理分级（r=0．61，Prs=0．01）有明显的相关性。结论AKAPl2基因启动子区出现的异常甲基化可导致其在膀胱移行细胞癌中的表达沉默，且与膀胱移行细胞癌的发生有关。
基金supported by the National Natural Science Foundation(Nos.81471958 and 31401258)the Natural Science Foundation of Shandong Province(No.ZR2012BM006),China
文摘Transcription factors, which represent an important class of proteins that play key roles in controlling cellular proliferation and cell cycle modulation, are attractive targets for cancer therapy. Previous researches have shown that the expression level of activating transcription factor 5 （ATF5） was frequently increased in glioma and its acetylation level was related to glioma. The purposes of this study were to explore the methylation level of ATF5 in clinical glioma tissues and to explore the effect of ATF5 methylation on the expression of ATF5 in glioma. Methylation of the promoter region of ATF5 was assayed by bisulflte-specific polymerase chain reaction （PCR） sequencing analysis in 35 cases of glioma and 5 normal tissues. Quantitative real-time PCR （qRT-PCR） was also performed to detect ATF5 mRNA expression in 35 cases of glioma and 5 normal tissues. Clinical data were collected from the patients and analyzed. The percentages of methylation of the ATF5 gene in the promoter region in healthy control, patients with well-differentiated glioma, and those with poorly differentiated glioma were 87.78%, 73.89%, and 47.70%, respectively. Analysis of the methylation status of the promoter region of the ATF5 gene showed a gradually de- creased methylation level in poorly differentiated glioma, well-differentiated glioma, and normal tissues （P〈0.05）. There was also a significant difference between well-differentiated glioma and poorly differentiated glioma （P〈0.05）. ATF5 mRNA expression in glioma was significantly higher than that in the normal tissues （P〈0.05）. This study provides the first evidence that the methylation level of ATF5 decreased, and its mRNA expression was evidently up-regulated in glioma.
