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ETS-2转录因子与启动子的+1^+40区结合是肝癌相关基因HCCS1的转录所必需
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作者 王鹏 毛大芩 +1 位作者 蓝斐 朱景德 《肿瘤》 CAS CSCD 北大核心 2006年第5期407-413,共7页
目的:阐明HCCS1基因启动子的转录调控机制。方法:引物延伸法确定HCCS1基因的转录起始点,通过限制性内切酶酶切介导对HCCS1基因全长启动子做进行性的5'缺失,用瞬时转染/双荧光素酶报告系统确定最小启动子,连接体扫描突变分析来确定... 目的:阐明HCCS1基因启动子的转录调控机制。方法:引物延伸法确定HCCS1基因的转录起始点,通过限制性内切酶酶切介导对HCCS1基因全长启动子做进行性的5'缺失,用瞬时转染/双荧光素酶报告系统确定最小启动子,连接体扫描突变分析来确定启动子功能的关键顺式序列区,电泳迁移率实验并附以抗体介导超迁移实验来确定关键的反式因子。结果:HCCS1基因的转录起始点被定位于-177/-178处的C残基(ATG为+1)。最小启动子位于-60^+148区(转录起始点为+1)之中。在关键的调控区(+1^+40)所含的已知顺式序列中有2个ETS转录因子识别序列,而不是p53或NF-κB,识别序列与其相应的转录因子(ETS-2)的结合有着重要的功能内涵。结论:ETS-2转录因子与启动子的+1^+40区中相应的顺式序列结合,在肝癌相关基因HCCS1的转录活性中起着关键作用。 展开更多
关键词 肝肿瘤 肝细胞 基因表达调控 基因 肿瘤抑制 基因 hccs1 SMMC-7721细胞
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Transcription of the putative tumor suppressor gene HCCS1 requires binding of ETS-2 to its consensus near the transcription start site 被引量:3
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作者 Jing De Zhu Qi Fei +4 位作者 Peng Wang Fei Lan Da Qin Mao Hong Yu Zhang Xue Biao Yao 《Cell Research》 SCIE CAS CSCD 2006年第9期780-796,共17页
The hepatocellular carcinoma suppressor 1 (HCCS1) gene was identified by both positional cloning from a predominant region of loss of heterozygosity (17p 13.3) in liver cancer and by functional screening for genes... The hepatocellular carcinoma suppressor 1 (HCCS1) gene was identified by both positional cloning from a predominant region of loss of heterozygosity (17p 13.3) in liver cancer and by functional screening for genes affecting cell proliferation in large-scale transfection assays. Its overexpression results in inhibition of cell proliferation in cell culture and tumor growth in nude mice. To understand its transcription regulation, the promoter architecture has been dissected in detail. The major start of transcription was mapped by primer extension to a C residue, 177 nucleotides upstream of the ATG codon. By assessing the promoter activity of a set of linker-scanning mutants of the minimal promoter (-60 to +148 region) in a transient transfection assay, we found that the +1 to + 40 region is critical to HCCS1 gene transcription, containing binding sites for transcription factors NF-kB (-21 to +7 and +40 to +26), p53 (+29 to +9) and ETS (+4 to +20 and +23 to +39). Biochemical and molecular analyses revealed that the ETS transcription factors ETS-2 and Elf-1 bind to the two ETS sites in situ and contribute significantly to the transcriptionally active state of the HCCS1 gene, while NF-kB, p53 and two other members of the ETS family (ETS-1 and NERF2) appear to play little role. Our observations provide insight into the mechanistic aspects of HCCS1 transcription regulation. 展开更多
关键词 hccs1 gene transcription regulation ETS p53 NF-KB
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HCCS1(hVPS53)在非小细胞肺癌中的表达及临床意义
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作者 林之枫 黄海龙 +2 位作者 屈潮强 吕帆真 沈晓咏 《中国癌症杂志》 CAS CSCD 北大核心 2011年第11期841-845,共5页
背景与目的:肝癌抑癌基因1(hepatocellular carcinoma suppressor 1,HCCS1)是酵母VPS53的同源基因,即人VPS53(hVPS53),位于染色体17p13.3区,在肝癌中表达降低。非小细胞肺癌(non-smallcell lung cancer,NSCLC)在染色体17p13.3区也存在... 背景与目的:肝癌抑癌基因1(hepatocellular carcinoma suppressor 1,HCCS1)是酵母VPS53的同源基因,即人VPS53(hVPS53),位于染色体17p13.3区,在肝癌中表达降低。非小细胞肺癌(non-smallcell lung cancer,NSCLC)在染色体17p13.3区也存在高杂合性缺失。本研究旨在探讨HCCS1(hVPS53)在NSCLC中的表达及其临床意义。方法:采用实时定量PCR检测HCCS1(hVPS53)mRNA在26例NSCLC癌及配对癌旁组织中的水平,采用免疫组织化学法检测HCCS1(hVPS53)蛋白在31例NSCLC癌及配对癌旁组织中的表达情况,并分析表达水平与NSCLC临床、病理特征的关系。结果:HCCS1(hVPS53)mRNA在肺癌组织中的表达水平为0.0044±0.0036;癌旁组织中为0.0067±0.0054。癌旁组织表达高于癌组织,差异有统计学意义(P=0.023)。HCCS1(hVPS53)蛋白在肺癌组织中的表达水平为4.67±1.15;癌旁组织中为6.13±1.24。癌旁组织表达高于癌组织,差异有统计学意义(P=0.038)。癌组织与癌旁组织HCCS1(hVPS53)mRNA和蛋白水平的差异与肿瘤淋巴结转移有关,有淋巴结转移的肿瘤mRNA和蛋白水平低于癌旁组织(P<0.05)。癌与癌旁HCCS1(hVPS53)mRNA和蛋白水平差异与病人性别、年龄、病理类型、TNM分期和肿瘤分级无关(P>0.05)。结论:癌组织中HCCS1(hVPS53)的mRNA和蛋白水平均比癌旁组织低,与肿瘤淋巴结转移有关,预示其在NSCLC的发生、发展中有一定的作用。 展开更多
关键词 肝癌抑癌基因1 表达水平 非小细胞肺癌
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肝细胞癌HCCS1基因突变和杂合缺失分析
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作者 李秋文 宋林萍 +2 位作者 朱建华 康欢荣 肖文华 《肿瘤学杂志》 CAS 2009年第10期914-916,共3页
[目的]进一步阐明HCCS1基因在肝细胞癌发病中的作用,研究肝细胞癌HCCS1基因突变和杂合缺失状态。[方法]采用PCR-SSCP杂合缺失分析和测序技术对62例肝细胞癌HCCS1基因突变和杂合缺失进行了检测。[结果]在62例肝细胞癌中无一例体细胞突变... [目的]进一步阐明HCCS1基因在肝细胞癌发病中的作用,研究肝细胞癌HCCS1基因突变和杂合缺失状态。[方法]采用PCR-SSCP杂合缺失分析和测序技术对62例肝细胞癌HCCS1基因突变和杂合缺失进行了检测。[结果]在62例肝细胞癌中无一例体细胞突变,但发现9个单核苷酸多态性。在56例杂合子中,各位点杂合缺失率从32.3%到46.9%不等。[结论]未能在来自西南地区的中国肝细胞癌患者中发现HCCS1突变,HCCS1基因在肝细胞癌发生发展过程中的作用尚需进一步研究。 展开更多
关键词 肝肿瘤 hccs1基因 突变 杂合缺失
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EFFECTS OF COOLED EXTERNAL EXHAUST GAS RECIRCULATION ON DIESEL HOMOGENEOUS CHARGE COMPRESSION IGNITION ENGINE 被引量:2
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作者 SHI Lei CUI Yi DENG Kangyao 《Chinese Journal of Mechanical Engineering》 SCIE EI CAS CSCD 2007年第1期21-24,共4页
The effects of cooled external exhaust gas recirculation (EGR) on the combustion and emission performance of diesel fuel homogeneous charge compression ignition (HCCI) are studied. Homogeneous mixture is formed by... The effects of cooled external exhaust gas recirculation (EGR) on the combustion and emission performance of diesel fuel homogeneous charge compression ignition (HCCI) are studied. Homogeneous mixture is formed by injecting fuel in-cylinder in the negative valve overlap (NVO) period. So, the HCCI combustion which has low NOx and smoke emission is achieved. Cooled external EGR can delay the start of combustion effectively, which is very useful for high cetane fuel (diesel) HCCI, because these fuels can easily self-ignition, which makes the start of combustion more early. External EGR can avoid the knock combustion of HCCI at high load which means that the EGR can expand the high load limit. HCCI maintains low smoke emission at various EGR rate and various load compared with conventional diesel engine because there is no fuel-rich area in cylinder. 展开更多
关键词 Homogeneous charge compression ignition (HCC1) Combustion Cooled exhaust gas recirculation (EGR) Emission
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