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
AIM:To investigate the relationship between expression of p21^(WAF1) and p53 gene,and to evaluate the deletion and polymorphism of p21^(WAF1) gene in gastric carcinoma (GC). METHODS:Expression of p21 and p53 proteins,...AIM:To investigate the relationship between expression of p21^(WAF1) and p53 gene,and to evaluate the deletion and polymorphism of p21^(WAF1) gene in gastric carcinoma (GC). METHODS:Expression of p21 and p53 proteins,and deletion and polymorphism of p21 gene in GC were examined by streptavidin-peroxidase conjugated method (SP) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) respectively. RESULTS:The expression of p21 and p53 was found in 100% (20/20) and 0% (0/20) of normal gastric mucosae (NGM),92.5% (37/40) and 15.0% (6/40) of dysplasia (DP) and 39.8% (43/108) and 56.5% (61/108) of GC,respectively. The positive rate of p21 in GC was lower than that in NGM and DP (P<0.05),while the positive rate of p53 in GC was higher than that in NGM end DP (P<0.05).p21 and p53 were significantly expressed in 63.3% (19/30) and 36.7% (11/30),35.0% (14/40) and 77.5% (31/40),26.7% (4/15) and 80.0% (12/15),30.8% (4/13) and 30.8% (4/13),and 20.0% (2/10) and 30.0%,(3/10) of well-differentiated, poorly-differentiated,undifferentiated carcinomas,mucoid carcinomas and signet ring cell carcinomas.The expression of p21 in well-differentiated carcinomas was significantly higher than that in poorly-differentiated,un-differentiated, mucoid carcinomas and signet ring cell carcinomas (P<0.05). Contrarily,The expression of p53 was increased from well- differentiated to poorly-differentiated and un-differentiated carcinomas (P<0.05).The expression of p21 and p53 in paired primary and metastatic GC (35.3% and 70.6%) was different from non-metastatic GC (62.5% and 42.5%) markedly (P<0.05).The expression of p21 in invasive superficial muscle (60.0%) was higher than that in invasive deep muscle or total layer (35.2%) (P<0.05) and was higher in TNM stages Ⅰ (60.0%) and Ⅱ (56.2%) than in stages Ⅲ (27.9%) and Ⅳ (22.2%) (P<0.05),whereas the expression of p53 did not correlate to invasion depth or TNM staging (P>0.05).The exoression patterns of p53+/p21-,and of p53-/p21+ were found in 5.0% and 82.5% of DP.There was a significant correlation between expression of p21 and p53 (P<0.05).But there was no significant correlation between expression of both in GC (P>0.05).There was no deletion in exon 2 of p21 gene in 30 cases of GC and 45 cases of non-GC,but polymorphism of p21 gene at exon 2 was found in 26.7% (8/30) of GC and 8.9% (4/45) of non- GC,a significant difference was found between GC and non-GC (P<0.05).There was no significant relation between p21 expression of polymorphism (37.5%,3/8) and non-polymorphism (45.5%,10/22) in GC (P>0.05). CONCLUSION:The loss of p21 protein and abnormal expression of p53 are related to carcinogenesis,differentiation and metastasis of GC.The expression of p21 is related to invasion and clinical staging in GC intimately.The expression of p21 protein depends on p53 protein largely in NGM and DP,but not in GC.No deletion of p21 gene in exon 2 can be found in GC.The polymorphism of p21 gene might be involved in gastric carcinogenesis.There is no significant association between polymorphism of p21 gene and expression of p21 protein.展开更多
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.
基金Supported by the Key Programs during the 8~(th)5-Year Plan Period,the Bureau of Health,Hunan Province, China, No. 9301
文摘AIM:To investigate the relationship between expression of p21^(WAF1) and p53 gene,and to evaluate the deletion and polymorphism of p21^(WAF1) gene in gastric carcinoma (GC). METHODS:Expression of p21 and p53 proteins,and deletion and polymorphism of p21 gene in GC were examined by streptavidin-peroxidase conjugated method (SP) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) respectively. RESULTS:The expression of p21 and p53 was found in 100% (20/20) and 0% (0/20) of normal gastric mucosae (NGM),92.5% (37/40) and 15.0% (6/40) of dysplasia (DP) and 39.8% (43/108) and 56.5% (61/108) of GC,respectively. The positive rate of p21 in GC was lower than that in NGM and DP (P<0.05),while the positive rate of p53 in GC was higher than that in NGM end DP (P<0.05).p21 and p53 were significantly expressed in 63.3% (19/30) and 36.7% (11/30),35.0% (14/40) and 77.5% (31/40),26.7% (4/15) and 80.0% (12/15),30.8% (4/13) and 30.8% (4/13),and 20.0% (2/10) and 30.0%,(3/10) of well-differentiated, poorly-differentiated,undifferentiated carcinomas,mucoid carcinomas and signet ring cell carcinomas.The expression of p21 in well-differentiated carcinomas was significantly higher than that in poorly-differentiated,un-differentiated, mucoid carcinomas and signet ring cell carcinomas (P<0.05). Contrarily,The expression of p53 was increased from well- differentiated to poorly-differentiated and un-differentiated carcinomas (P<0.05).The expression of p21 and p53 in paired primary and metastatic GC (35.3% and 70.6%) was different from non-metastatic GC (62.5% and 42.5%) markedly (P<0.05).The expression of p21 in invasive superficial muscle (60.0%) was higher than that in invasive deep muscle or total layer (35.2%) (P<0.05) and was higher in TNM stages Ⅰ (60.0%) and Ⅱ (56.2%) than in stages Ⅲ (27.9%) and Ⅳ (22.2%) (P<0.05),whereas the expression of p53 did not correlate to invasion depth or TNM staging (P>0.05).The exoression patterns of p53+/p21-,and of p53-/p21+ were found in 5.0% and 82.5% of DP.There was a significant correlation between expression of p21 and p53 (P<0.05).But there was no significant correlation between expression of both in GC (P>0.05).There was no deletion in exon 2 of p21 gene in 30 cases of GC and 45 cases of non-GC,but polymorphism of p21 gene at exon 2 was found in 26.7% (8/30) of GC and 8.9% (4/45) of non- GC,a significant difference was found between GC and non-GC (P<0.05).There was no significant relation between p21 expression of polymorphism (37.5%,3/8) and non-polymorphism (45.5%,10/22) in GC (P>0.05). CONCLUSION:The loss of p21 protein and abnormal expression of p53 are related to carcinogenesis,differentiation and metastasis of GC.The expression of p21 is related to invasion and clinical staging in GC intimately.The expression of p21 protein depends on p53 protein largely in NGM and DP,but not in GC.No deletion of p21 gene in exon 2 can be found in GC.The polymorphism of p21 gene might be involved in gastric carcinogenesis.There is no significant association between polymorphism of p21 gene and expression of p21 protein.
