Reduced p21(WAF1/CIP1) expression and p53 mutation in hepatocellular carcinomas

被引:77
作者
Hui, AM [1 ]
Kanai, Y [1 ]
Sakamoto, M [1 ]
Tsuda, H [1 ]
Hirohashi, S [1 ]
机构
[1] NATL CANC CTR,RES INST,DIV PATHOL,CHUO KU,TOKYO 104,JAPAN
关键词
D O I
10.1002/hep.510250314
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
p21(WAF1/CIP1) is a universal cyclin-dependent kinase (cdk) inhibitor, the expression of which is regulated by p53-dependent and p53-independent pathways. We examined p21(WAF1/CIP1) expression in and p53 status of 21 primary hepatocellular carcinomas (HCCs) by reverse-transcriptase polymerase chain reaction (RT-PCR) and by PCR single-strand conformation polymorphism (PCR-SSCP) analysis. p21(WAF1/CIP1) messenger RNA expression was reduced markedly in 8 of 21 HCCs (38.1%) and 5 of these 8 HCCs bore p53 mutations. The relative p21(WAF1/CIP1) messenger RNA expression value of HCCs with p53 mutations (.73 +/- .13 U, n = 6) was significantly lower than that of HCCs with wild-type p53 (1.00 +/- 0.21 U, n = 14; P < .01). The p21(WAF1/CIP1) expression levels in cancerous tissues (.73 +/- .13 U) were significantly reduced in comparison with those in noncancerous tissues (.97 +/- .13 U) (P < .01) in the 6 cases with p53 mutations. These data indicate that p21(WAF1/CIP1) expression in HCCs is predominantly regulated by dependence on p53 and that reduced p21(WAF1/CIP1) expression may participate in hepatocarcinogenesis.
引用
收藏
页码:575 / 579
页数:5
相关论文
共 41 条
[21]   CLONING OF SENESCENT CELL-DERIVED INHIBITORS OF DNA-SYNTHESIS USING AN EXPRESSION SCREEN [J].
NODA, A ;
NING, Y ;
VENABLE, SF ;
PEREIRASMITH, OM ;
SMITH, JR .
EXPERIMENTAL CELL RESEARCH, 1994, 211 (01) :90-98
[22]   ORDERING S-PHASE AND M-PHASE IN THE CELL-CYCLE [J].
NURSE, P .
CELL, 1994, 79 (04) :547-550
[23]  
ODA T, 1992, CANCER RES, V52, P3674
[24]  
ODA T, 1992, CANCER RES, V52, P6358
[25]  
Ozcelik H, 1995, CLIN CANCER RES, V1, P907
[26]   JOINING THE COMPLEX - CYCLIN-DEPENDENT KINASE INHIBITORY PROTEINS AND THE CELL-CYCLE [J].
PETER, M ;
HERSKOWITZ, I .
CELL, 1994, 79 (02) :181-184
[27]   G1 PHASE PROGRESSION - CYCLING ON CUE [J].
SHERR, CJ .
CELL, 1994, 79 (04) :551-555
[28]   ABSENCE OF WAF1 MUTATIONS IN A VARIETY OF HUMAN MALIGNANCIES [J].
SHIOHARA, M ;
ELDEIRY, WS ;
WADA, M ;
NAKAMAKI, T ;
TAKEUCHI, S ;
YANG, R ;
CHEN, DL ;
VOGELSTEIN, B ;
KOEFFLER, HP .
BLOOD, 1994, 84 (11) :3781-3784
[29]   INHIBITION OF MYOGENIC DIFFERENTIATION IN PROLIFERATING MYOBLASTS BY CYCLIN D1-DEPENDENT KINASE [J].
SKAPEK, SX ;
RHEE, J ;
SPICER, DB ;
LASSAR, AB .
SCIENCE, 1995, 267 (5200) :1022-1024
[30]  
STEINMAN RA, 1994, ONCOGENE, V9, P3389