Modulation of p53, WAF1/p21 and BCL-2 expression during retinoic acid-induced differentiation of NB4 promyelocytic cells

被引:32
作者
Bocchia, M [1 ]
Xu, Q [1 ]
Wesley, U [1 ]
Xu, Y [1 ]
Korontsvit, T [1 ]
Loganzo, F [1 ]
Albino, AP [1 ]
Scheinberg, DA [1 ]
机构
[1] MEM SLOAN KETTERING CANC CTR,LEUKEMIA SERV,NEW YORK,NY 10021
关键词
NB4; cells; retinoic acid; p53; WAF1/p21; BCL-2; apoptosis;
D O I
10.1016/S0145-2126(96)00085-9
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The NB4 cell line, established from a patient with APL, carries the t(15;17) and undergoes differentiation along the granulocytic pathway when exposed to retinoic acid (RA). The NB4 cell line was used as a model for exploring the expression of genes and proteins implicated in growth regulation, differentiation and apoptosis during treatment with RA. NB4 cells undergo a series of cytological and molecular alterations during RA treatment--Day 1: cell differentiation marked by an increase in CD11b is evident. Day 2: WAF1/p21 mRNA and then protein rise, though they drop 2 days later. Day 3: the percentage of cells in S phase begins to decrease and G1 arrest begins. Day 4: p53 mRNA level and then protein levels fall. Day 5: CD11b/BCL-2 double staining cells are markedly reduced. No signs of apoptosis were observed after up to 8 days of treatment with RA. These results demonstrate that NB4 cells treated with RA rapidly differentiate and arrest at G1 phase concurrent with p53-independent WAF1/p21 induction; in addition, phenotypic differentiation appears to commence before changes in cell cycle progression. An explanation for the decrease in p53 as well as the lack of apoptosis immediately after BCL-2 downregulation will require further study. (C) 1997 Elsevier Science Ltd.
引用
收藏
页码:439 / 447
页数:9
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