目的:探讨转录因子21(transcription factor 21,TCF21)对喉癌细胞株Hep-2生物学特性的影响及其相关的作用机制。方法:利用慢病毒转染技术外源性过表达喉癌Hep-2细胞中的TCF21,然后分别采用细胞增殖检测(Cell Counting Kit-8,CCK-8)法和...目的:探讨转录因子21(transcription factor 21,TCF21)对喉癌细胞株Hep-2生物学特性的影响及其相关的作用机制。方法:利用慢病毒转染技术外源性过表达喉癌Hep-2细胞中的TCF21,然后分别采用细胞增殖检测(Cell Counting Kit-8,CCK-8)法和流式细胞术检测细胞增殖及凋亡能力的变化;Western印迹检测周期及凋亡相关蛋白的表达。结果:在Hep-2细胞中过表达TCF21后,细胞的增殖能力显著降低,周期进程缓慢,而细胞凋亡显著增加;Transwell细胞迁移实验显示过表达TCF21可抑制Hep-2细胞迁移。Western印迹实验结果显示过表达TCF21后,cyclin D1,CDK4,CDK6,p-R b及b c l-2的蛋白表达水平显著下降;P 2 1和Ba x及c l eaved-c a s pa s e-3的蛋白表达水平显著升高。结论:人喉癌细胞株Hep-2中,过表达TCF21可通过调控周期及凋亡相关因子的表达,发挥增殖抑制及凋亡促进作用,提示TCF21可作为诊断和靶向治疗喉癌的潜在作用位点。展开更多
Cell cycle progression is regulated by interactions between cyclins and cyclin-dependent kinases (CDKs). p21(WAF1) is one of the CIP/KIP family which inhibits CDKs activity. Increased expression of p21(WAF1) may play ...Cell cycle progression is regulated by interactions between cyclins and cyclin-dependent kinases (CDKs). p21(WAF1) is one of the CIP/KIP family which inhibits CDKs activity. Increased expression of p21(WAF1) may play an important role in the growth arrest induced in transformed cells. Although the stability of the p21( WAF1) mRNA could be altered by different signals, cell differentiation and numerous influencing factors. However, recent studies suggest that two known mechanisms of epigenesis, i.e.gene inactivation by methylation in promoter region and changes to an inactive chromatin by histone deacetylation, seem to be the best candidate mechanisms for inactivation of p21( WAF1). To date, almost no coding region p21(WAF1) mutations have been found in tumor cells, despite extensive screening of hundreds of various tumors. Hypermethylation of the p21(WAF1) promoter region may represent an alternative mechanism by which the p21(WAF1/CIP1) gene can be inactivated. The reduction of cellular DNMT protein levels also induces a corresponding rapid increase in the cell cycle regulator p21(WAF1) protein demonstrating a regulatory link between DNMT and p21(WAF1) which is independent of methylation of DNA. Both histone hyperacetylation and hypoacetylation appear to be important in the carcinoma process, and induction of the p21(WAF1) gene by histone hyperacetylation may be a mechanism by which dietary fiber prevents carcinogenesis. Here, we review the influence of histone acetylation and DNA methylation on p21(WAF1) transcription, and affection of pathways or factors associated such as p 53, E2A, Sp1 as well as several histone deacetylation inhibitors.展开更多
文摘目的:探讨转录因子21(transcription factor 21,TCF21)对喉癌细胞株Hep-2生物学特性的影响及其相关的作用机制。方法:利用慢病毒转染技术外源性过表达喉癌Hep-2细胞中的TCF21,然后分别采用细胞增殖检测(Cell Counting Kit-8,CCK-8)法和流式细胞术检测细胞增殖及凋亡能力的变化;Western印迹检测周期及凋亡相关蛋白的表达。结果:在Hep-2细胞中过表达TCF21后,细胞的增殖能力显著降低,周期进程缓慢,而细胞凋亡显著增加;Transwell细胞迁移实验显示过表达TCF21可抑制Hep-2细胞迁移。Western印迹实验结果显示过表达TCF21后,cyclin D1,CDK4,CDK6,p-R b及b c l-2的蛋白表达水平显著下降;P 2 1和Ba x及c l eaved-c a s pa s e-3的蛋白表达水平显著升高。结论:人喉癌细胞株Hep-2中,过表达TCF21可通过调控周期及凋亡相关因子的表达,发挥增殖抑制及凋亡促进作用,提示TCF21可作为诊断和靶向治疗喉癌的潜在作用位点。
文摘Cell cycle progression is regulated by interactions between cyclins and cyclin-dependent kinases (CDKs). p21(WAF1) is one of the CIP/KIP family which inhibits CDKs activity. Increased expression of p21(WAF1) may play an important role in the growth arrest induced in transformed cells. Although the stability of the p21( WAF1) mRNA could be altered by different signals, cell differentiation and numerous influencing factors. However, recent studies suggest that two known mechanisms of epigenesis, i.e.gene inactivation by methylation in promoter region and changes to an inactive chromatin by histone deacetylation, seem to be the best candidate mechanisms for inactivation of p21( WAF1). To date, almost no coding region p21(WAF1) mutations have been found in tumor cells, despite extensive screening of hundreds of various tumors. Hypermethylation of the p21(WAF1) promoter region may represent an alternative mechanism by which the p21(WAF1/CIP1) gene can be inactivated. The reduction of cellular DNMT protein levels also induces a corresponding rapid increase in the cell cycle regulator p21(WAF1) protein demonstrating a regulatory link between DNMT and p21(WAF1) which is independent of methylation of DNA. Both histone hyperacetylation and hypoacetylation appear to be important in the carcinoma process, and induction of the p21(WAF1) gene by histone hyperacetylation may be a mechanism by which dietary fiber prevents carcinogenesis. Here, we review the influence of histone acetylation and DNA methylation on p21(WAF1) transcription, and affection of pathways or factors associated such as p 53, E2A, Sp1 as well as several histone deacetylation inhibitors.
