Modulation of p53, WAF1/p21 and BCL-2 expression during retinoic acid-induced differentiation of NB4 promyelocytic cells
Modulation of p53, WAF1/p21 and BCL-2 expression during retinoic acid-induced differentiation of NB4 promyelocytic cells
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DOI：
10.1016/s0145-2126(96)00085-9
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发表时间：
1997-05-01
影响因子：
2.7
通讯作者：
Scheinberg, DA
中科院分区：
文献类型：
--
作者：
Bocchia, M;Xu, Q;Scheinberg, DA
从APL患者建立的NB 4细胞系携带t（15;17），并且当暴露于视黄酸（RA）时，其沿着粒细胞途径沿着分化。NB 4细胞系被用作探索在用RA治疗期间与生长调节、分化和凋亡有关的基因和蛋白质表达的模型。NB 4细胞在RA治疗期间经历一系列细胞学和分子学改变-第1天：以CD 11b增加为标志的细胞分化是明显的。第2天：WAF 1/p21 mRNA和蛋白质升高，但2天后下降。第3天：S期细胞百分比开始下降，G1期阻滞开始。第4天：p53 mRNA水平下降，然后蛋白质水平下降。第5天：CD 11b/BCL-2双染细胞明显减少。RA治疗8天后未观察到细胞凋亡迹象。这些结果表明，RA处理的NB 4细胞迅速分化，并在G1期与p53-非依赖性WAF 1/p21诱导同步逮捕;此外，表型分化似乎开始细胞周期进展的变化之前。对p53减少以及BCL-2下调后立即缺乏凋亡的解释需要进一步研究。(C)1997 Elsevier Science Ltd.
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.