Gene expression profiling during all-trans retinoic acid-induced cell differentiation of acute promyelocytic leukemia cells
Gene expression profiling during all-trans retinoic acid-induced cell differentiation of acute promyelocytic leukemia cells
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DOI：
10.1016/s1525-1578(10)60476-x
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发表时间：
2003-11-01
影响因子：
4.1
通讯作者：
She, JX
中科院分区：
文献类型：
--
作者：
Yang, LJ;Zhao, HS;She, JX
利用基因芯片技术，我们研究了全反式维甲酸(ATRA)诱导的人急性早幼粒细胞白血病(APL)细胞株NB4分化过程中基因表达的变化。分析ATRA作用12小时、24小时、48小时、72小时和96小时后NB4细胞中12,288个基因的表达。在这段时间里，我们发现了168个上调基因和179多个下调基因，其中大多数以前没有报道过。许多改变的基因编码产物，参与信号通路、细胞分化、细胞程序性死亡、转录调节以及细胞因子和趋化因子的产生。值得注意的是，CD52和蛋白激酶A调节亚单位α(PKA-R1pha)基因，其产物在目前正在进行的临床试验中被用作某些人类肿瘤的治疗靶点，是观察到在ATRA治疗后显著上调的基因之一。本研究为进一步了解ATRA诱导APL细胞分化的机制提供了有价值的数据，并提出了潜在的治疗方案。
Using cDNA microarrays we determined the gene expression patterns in the human acute promyelocytic leukemia (APL) cell line NB4 during all-trans; retinoic acid (ATRA)-induced differentiation. We analyzed the expression of 12,288 genes in the NB4 cells after 12 hours, 24 hours, 48 hours, 72 hours, and 96 hours of ATRA exposure. During this time course, we found 168 up-regulated and more than 179 down-regulated genes, most of which have not been reported before. Many of the altered genes encode products that participate in signaling pathways, cell differentiation, programmed cell death, transcription regulation, and production of cytokines and chemokines. Of interest, the CD52 and protein kinase A regulatory subunit alpha (PKA-R1alpha) genes, whose products are being used as therapeutic targets for certain human neoplasias in currently ongoing clinical trials, were among the genes observed to be markedly up-regulated after ATRA treatment. The present study provides valuable data to further understand the mechanism of ATRA-induced APL cell differentiation and suggests potential therapeutic alternatives for this leukemia.