目的:探讨生长抑制基因(inhibitor of growth,p33ING1)在结直肠癌中的表达意义,以及p33ING1与结直肠癌临床病理特征的关系及其可能的作用机制。方法:对60例结直肠癌组织及20例癌旁非肿瘤组织标本,应用免疫组化检测肿瘤组织和正常组织的p...目的:探讨生长抑制基因(inhibitor of growth,p33ING1)在结直肠癌中的表达意义,以及p33ING1与结直肠癌临床病理特征的关系及其可能的作用机制。方法:对60例结直肠癌组织及20例癌旁非肿瘤组织标本,应用免疫组化检测肿瘤组织和正常组织的p33ING1、p21WAF1的表达。结果:p33ING1在结直肠癌组织中的表达阳性率为43.3%,在正常组织中为90.0%,显著低于正常组织(P<0.005);p33ING1减低与结直肠癌的Dukes分期及淋巴结转移有一定关系(P<0.005和P<0.01),而与患者的性别、年龄、肿瘤分化程度、肿瘤部位及浸润深度无明显关系(P>0.05)。p33ING1与p21WAF1表达呈正相关关系(P<0.05)。结论:p33ING1在结直肠癌组织中低表达,对结直肠癌的发生、发展可能起着重要的作用;p33ING1、p21WAF1表达可作为判断结直肠癌恶性程度的重要指标之一。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:探讨生长抑制基因(inhibitor of growth,p33ING1)在结直肠癌中的表达意义,以及p33ING1与结直肠癌临床病理特征的关系及其可能的作用机制。方法:对60例结直肠癌组织及20例癌旁非肿瘤组织标本,应用免疫组化检测肿瘤组织和正常组织的p33ING1、p21WAF1的表达。结果:p33ING1在结直肠癌组织中的表达阳性率为43.3%,在正常组织中为90.0%,显著低于正常组织(P<0.005);p33ING1减低与结直肠癌的Dukes分期及淋巴结转移有一定关系(P<0.005和P<0.01),而与患者的性别、年龄、肿瘤分化程度、肿瘤部位及浸润深度无明显关系(P>0.05)。p33ING1与p21WAF1表达呈正相关关系(P<0.05)。结论:p33ING1在结直肠癌组织中低表达,对结直肠癌的发生、发展可能起着重要的作用;p33ING1、p21WAF1表达可作为判断结直肠癌恶性程度的重要指标之一。
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.
