Microarray analysis uncovers retinoid targets in human bronchial epithelial cells
Microarray analysis uncovers retinoid targets in human bronchial epithelial cells
复制标题
DOI：
10.1038/sj.onc.1206728
复制
发表时间：
2003-07-31
期刊：
影响因子：
8
通讯作者：
Dmitrovsky, E
中科院分区：
文献类型：
--
作者：
Ma, Y;Koza-Taylor, PH;Dmitrovsky, E
类维生素A是维生素A的天然和合成衍生物，在癌症治疗和预防中发挥作用。有必要揭示解释类维生素A反应或抗性的机制。本研究确定了与BEAS-2B人支气管上皮细胞生长抑制相关的候选全反式维甲酸（RA）靶基因。微阵列分析使用Affyssin阵列进行。通过逆转录聚合酶链反应（RT-PCR），Western或北方分析，共11个RA诱导的物种进行了验证。这些物种中的三个是新的候选RA靶基因在人支气管上皮细胞。这些包括：胎盘骨形态发生蛋白（PLAB），多胺氧化酶亚型1（PAOh1）和E74样因子3（ELF3）。在RA抗性BEAS-2BR1细胞中研究了表达模式。在BEAS-2B-R1细胞中，RA使假定的淋巴细胞G0/G1转换基因（G0S2）、血红素加氧酶1（HMOX1）、肿瘤坏死因子-α-诱导蛋白2（TNFAIP2）、DNA结合抑制因子1（Id1）、fos样抗原1（FOSL 1）、转氨酶2（TGM2）、天冬酰胺合成酶（ASNS）、PLAB、PAOh1和ELF3的表达失调，而胰岛素样生长因子结合蛋白6（IGFBP6）的显著诱导仍然发生。总之，本研究在人支气管上皮细胞中鉴定了11个候选RA靶基因，包括3个新物种。在BEAS-2B-R1细胞中的表达研究表明，有几个直接参与RA信号传导，因为它们的异常表达与人支气管上皮细胞的RA抗性有关。
Retinoids, the natural and synthetic derivatives of vitamin A, have a role in cancer treatment and prevention. There is a need to reveal mechanisms that account for retinoid response or resistance. This study identified candidate all-trans-retinoic acid (RA) target genes linked to growth suppression in BEAS-2B human bronchial epithelial cells. Microarray analyses were performed using Affymetrix arrays. A total of 11 RA-induced species were validated by reverse transcription polymerase chain reaction (RT-PCR), Western or Northern analyses. Three of these species were novel candidate RA-target genes in human bronchial epithelial cells. These included: placental bone morphogenetic protein (PLAB), polyamine oxidase isoform 1 (PAOh1) and E74-like factor 3 (ELF3). Expression patterns were studied in RA-resistant BEAS-2BR1 cells. In BEAS-2B-R1 cells, RA dysregulated the expression of the putative lymphocyte G0/G1 switch gene (G0S2), heme oxygenase 1 (HMOX1), tumor necrosis factor-alpha-induced protein 2 (TNFAIP2), inhibitor of DNA binding 1(Id1), fos-like antigen 1 (FOSL1), transglutaminase 2 (TGM2), asparagine synthetase (ASNS), PLAB, PAOh1 and ELF3, while prominent induction of insulin-like growth-factor-binding protein 6 (IGFBP6) still occurred. In summary, this study identified 11 candidate RA-target genes in human bronchial epithelial cells including three novel species. Expression studies in BEAS-2B-R1 cells indicated that several were directly implicated in RA signaling, since their aberrant expression was linked to RA resistance of human bronchial epithelial cells.