P21Waf1/Cip1 is a potent cyclin-dependent kinase inhibitor. As a downstream mediator of p53, p21Waf1/Cip1 involves in cell cycle arrest, differentiation and apoptosis. Previous studies in human cells provided evidence...P21Waf1/Cip1 is a potent cyclin-dependent kinase inhibitor. As a downstream mediator of p53, p21Waf1/Cip1 involves in cell cycle arrest, differentiation and apoptosis. Previous studies in human cells provided evidence for a link between p21Waf1/Cip1 and cellular senescence. While in murine cells, the role of p21Waf1/Cip1 is indefinite. We explored this issue using NIH3T3 cells with inducible p21Waf1/Cip1 expression. Induction of p21Waf1/Cip1 triggered G1 growth arrest, and NIH3T3-p21 cells exhibited morphologic features, such as enlarged and flattened cellular shape, specific to the senescence phenotype. We also showed that p21Waf1/Cip1-transduced NIH3T3 cells expressed β-galactosidase activity at pH 6.0, which is known to be a marker of senescence. Our results suggest that p21Waf1/Cip1 can also induce senescence-like changes in murine cells.展开更多
p21 WAF1/CIP1 gene is known for a most important cell cycle regulator as well as its roles in apoptosis and differentiation. This review focuses on p21 WAF1/CIP1 gene functions and its association with carcinogenesis....p21 WAF1/CIP1 gene is known for a most important cell cycle regulator as well as its roles in apoptosis and differentiation. This review focuses on p21 WAF1/CIP1 gene functions and its association with carcinogenesis. Better understanding of the structure and function of p21 WAF1/CIP1 gene may help to comprehend molecular mechanisms of cancers and to facilitate diagnosis and treatment of malignancy.展开更多
Summary: P21 WAF1/Cip1 , an inhibitor of cyclin dependent kinases, is a critical downstream effector in the P53 specfic pathway of growth control. Increased expression of P21 WAF1/Cip1 has been found to ref...Summary: P21 WAF1/Cip1 , an inhibitor of cyclin dependent kinases, is a critical downstream effector in the P53 specfic pathway of growth control. Increased expression of P21 WAF1/Cip1 has been found to reflect the status of the P53 tumor suppressor pathway. We investigated the expression of P21 WAF1/Cip1 in a relatively small, but well characterized group consisting of 28 hepatocellular carcinomas. The samples were previously studied for P53 gene mutation. P21 WAF1/Cip1 expression were identified by in situ hybridization and immunohistochemistry. Positive ISH for P21 WAF1/Cip1 transcripts was found in 18 of 28 cases (64.3 %). All positive cases by ISH showed detectable P21 WAF1/Cip1 protein reactivity by IHC. No relationship was found between P21 WAF1/Cip1 staining and P53 mutational status. No associations were seen with tumor metastasis, size and tumor grade, except for tumor differentiation status which showed higher frequency of P21 WAF1/Cip1 expression in moderate well differentiated HCCs than poorly differentiated tumors ( P <0.05). It is concluded that expression of P21 WAF1/Cip1 is common in HCCs, but does not correlate with P53 mutational status or pathological parameters investigated except for tumor differentiation. Also, there may be other factors beside P53 that regulate P21 WAF1/Cip1 gene expression in HCCs.展开更多
基金We thank Dr. Gordon Peters of Imperial CancerResearch Fund for providing p21(Waf1/Cip1) cDNA,Dr. Hong-Bing Shu of National Jewish Medica1and Reearch Center for pRetro-on-Bax and 293-10A1 packaging line. We also thank Drs. WeiTAO and Zhi Gang LU
文摘P21Waf1/Cip1 is a potent cyclin-dependent kinase inhibitor. As a downstream mediator of p53, p21Waf1/Cip1 involves in cell cycle arrest, differentiation and apoptosis. Previous studies in human cells provided evidence for a link between p21Waf1/Cip1 and cellular senescence. While in murine cells, the role of p21Waf1/Cip1 is indefinite. We explored this issue using NIH3T3 cells with inducible p21Waf1/Cip1 expression. Induction of p21Waf1/Cip1 triggered G1 growth arrest, and NIH3T3-p21 cells exhibited morphologic features, such as enlarged and flattened cellular shape, specific to the senescence phenotype. We also showed that p21Waf1/Cip1-transduced NIH3T3 cells expressed β-galactosidase activity at pH 6.0, which is known to be a marker of senescence. Our results suggest that p21Waf1/Cip1 can also induce senescence-like changes in murine cells.
文摘p21 WAF1/CIP1 gene is known for a most important cell cycle regulator as well as its roles in apoptosis and differentiation. This review focuses on p21 WAF1/CIP1 gene functions and its association with carcinogenesis. Better understanding of the structure and function of p21 WAF1/CIP1 gene may help to comprehend molecular mechanisms of cancers and to facilitate diagnosis and treatment of malignancy.
文摘Summary: P21 WAF1/Cip1 , an inhibitor of cyclin dependent kinases, is a critical downstream effector in the P53 specfic pathway of growth control. Increased expression of P21 WAF1/Cip1 has been found to reflect the status of the P53 tumor suppressor pathway. We investigated the expression of P21 WAF1/Cip1 in a relatively small, but well characterized group consisting of 28 hepatocellular carcinomas. The samples were previously studied for P53 gene mutation. P21 WAF1/Cip1 expression were identified by in situ hybridization and immunohistochemistry. Positive ISH for P21 WAF1/Cip1 transcripts was found in 18 of 28 cases (64.3 %). All positive cases by ISH showed detectable P21 WAF1/Cip1 protein reactivity by IHC. No relationship was found between P21 WAF1/Cip1 staining and P53 mutational status. No associations were seen with tumor metastasis, size and tumor grade, except for tumor differentiation status which showed higher frequency of P21 WAF1/Cip1 expression in moderate well differentiated HCCs than poorly differentiated tumors ( P <0.05). It is concluded that expression of P21 WAF1/Cip1 is common in HCCs, but does not correlate with P53 mutational status or pathological parameters investigated except for tumor differentiation. Also, there may be other factors beside P53 that regulate P21 WAF1/Cip1 gene expression in HCCs.
