In a total of 83 UN specimens were investigated for proto-oncogene mutations, tumor supressor genes promoter methylation status and c-myc and Ki-67 expression. Point mutations in c-myc were detected in cases with high...In a total of 83 UN specimens were investigated for proto-oncogene mutations, tumor supressor genes promoter methylation status and c-myc and Ki-67 expression. Point mutations in c-myc were detected in cases with high grade and proliferation index. Mutated K-ras proto-onco- gene profiles were detected in 17 (21%) tumoral spiecemens that examined. Tumor specimens were also showed hypermethylated promoter domain for the SFRP2, MGMT tumor supressor genes. These findings showed the combine effect of mutated c-myc and K-ras oncogene and epigenetic inactivation of tissue specific tumor supressor genes (TS) play a crucial role in tumor progression and recurrence in UN carcinogenesis.展开更多
目的:研究髓母细胞瘤患者中发现的Supressor of Fused(Sufu)的突变位点与Sonic Hedgehog(Shh)信号通路异常激活之间的联系,从而揭示其与肿瘤生长发展之间的关系。方法:构建Sufu突变位点的表达质粒,通过定量PCR、蛋白免疫印迹实验检测Suf...目的:研究髓母细胞瘤患者中发现的Supressor of Fused(Sufu)的突变位点与Sonic Hedgehog(Shh)信号通路异常激活之间的联系,从而揭示其与肿瘤生长发展之间的关系。方法:构建Sufu突变位点的表达质粒,通过定量PCR、蛋白免疫印迹实验检测Sufu突变体对Sufu^(-/-)细胞内源性Gli1表达水平的影响;通过免疫共沉淀检测Sufu突变体蛋白与Gli1的结合情况;通过MTT实验检测Sufu突变体对人髓母细胞瘤细胞(DAOY)生长增殖的影响。结果:定量PCR和蛋白免疫印迹实验发现,过表达Sufu的错义突变体(突变位点H87R)的Sufu^(-/-)细胞中内源性Gli1表达水平接近于过表达野生型Sufu的Sufu^(-/-)细胞,而过表达3个截短突变体(突变位点R146X、R299X、W430X)Sufu^(-/-)细胞中内源性Gli1表达水平相比于野生型明显增高。正常情况下野生型Sufu可以和Gli1蛋白结合,免疫共沉淀实验发现Sufu的突变体都不同程度地破坏了与Gli1蛋白的结合;蛋白周转速率实验发现Sufu的突变体可以通过蛋白酶体途径降解;MTT实验发现Sufu突变体失去了抑制DAOY细胞生长增殖的能力。结论:髓母细胞瘤患者身上观测到的Sufu突变位点可以驱动肿瘤的形成和生长,并通过细胞功能实验证实了Sufu通过结合Gli蛋白从而抑制其功能。展开更多
MAJOR POINTS OF THE COMMENTED ARTICLECumulative loss of heterozygosity(LOH)ofchromosomal regions and tumor suppressor geneshas been reported in hepatocellular carcinomas(HCCs) from China,Japan,and Korea.In thisissue o...MAJOR POINTS OF THE COMMENTED ARTICLECumulative loss of heterozygosity(LOH)ofchromosomal regions and tumor suppressor geneshas been reported in hepatocellular carcinomas(HCCs) from China,Japan,and Korea.In thisissue of the World Journal of Gastroenterology,Martins et al report an analysis of LOH andmicrosatellite instability in HCCs from a group of展开更多
文摘In a total of 83 UN specimens were investigated for proto-oncogene mutations, tumor supressor genes promoter methylation status and c-myc and Ki-67 expression. Point mutations in c-myc were detected in cases with high grade and proliferation index. Mutated K-ras proto-onco- gene profiles were detected in 17 (21%) tumoral spiecemens that examined. Tumor specimens were also showed hypermethylated promoter domain for the SFRP2, MGMT tumor supressor genes. These findings showed the combine effect of mutated c-myc and K-ras oncogene and epigenetic inactivation of tissue specific tumor supressor genes (TS) play a crucial role in tumor progression and recurrence in UN carcinogenesis.
文摘目的:研究髓母细胞瘤患者中发现的Supressor of Fused(Sufu)的突变位点与Sonic Hedgehog(Shh)信号通路异常激活之间的联系,从而揭示其与肿瘤生长发展之间的关系。方法:构建Sufu突变位点的表达质粒,通过定量PCR、蛋白免疫印迹实验检测Sufu突变体对Sufu^(-/-)细胞内源性Gli1表达水平的影响;通过免疫共沉淀检测Sufu突变体蛋白与Gli1的结合情况;通过MTT实验检测Sufu突变体对人髓母细胞瘤细胞(DAOY)生长增殖的影响。结果:定量PCR和蛋白免疫印迹实验发现,过表达Sufu的错义突变体(突变位点H87R)的Sufu^(-/-)细胞中内源性Gli1表达水平接近于过表达野生型Sufu的Sufu^(-/-)细胞,而过表达3个截短突变体(突变位点R146X、R299X、W430X)Sufu^(-/-)细胞中内源性Gli1表达水平相比于野生型明显增高。正常情况下野生型Sufu可以和Gli1蛋白结合,免疫共沉淀实验发现Sufu的突变体都不同程度地破坏了与Gli1蛋白的结合;蛋白周转速率实验发现Sufu的突变体可以通过蛋白酶体途径降解;MTT实验发现Sufu突变体失去了抑制DAOY细胞生长增殖的能力。结论:髓母细胞瘤患者身上观测到的Sufu突变位点可以驱动肿瘤的形成和生长,并通过细胞功能实验证实了Sufu通过结合Gli蛋白从而抑制其功能。
文摘MAJOR POINTS OF THE COMMENTED ARTICLECumulative loss of heterozygosity(LOH)ofchromosomal regions and tumor suppressor geneshas been reported in hepatocellular carcinomas(HCCs) from China,Japan,and Korea.In thisissue of the World Journal of Gastroenterology,Martins et al report an analysis of LOH andmicrosatellite instability in HCCs from a group of
