All-trans retinoic acid treatment of Wilms tumor cells reverses expression of genes associated with high risk and relapse in vivo
All-trans retinoic acid treatment of Wilms tumor cells reverses expression of genes associated with high risk and relapse in vivo
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DOI：
10.1038/sj.onc.1208725
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发表时间：
2005-08-01
期刊：
影响因子：
8
通讯作者：
Gessler, M
中科院分区：
文献类型：
--
作者：
Zirn, B;Samans, B;Gessler, M
肾母细胞瘤是儿童最常见的肿瘤之一。我们先前在一系列Wilms肿瘤中的微阵列筛选揭示了几个在晚期肿瘤中失调的候选基因，它们是视黄酸信号通路的一部分。为了研究维甲酸是否可以作为一种新的治疗药物在这些肿瘤中，我们处理培养的肾母细胞瘤细胞与不同浓度的全反式维甲酸（ATRA）和评估基因表达的变化，实时RT-PCR以及微阵列分析。先前发现在晚期肿瘤中失调的几个基因，如RARRES 1、RARRES 3、CTGF、CKS 2、CCNA 2、IGFBP 3、UBE 2C、CCL 2或ITM 2B，在ATRA治疗后表现出相反的表达变化。除了增强类维生素A信号传导，转化生长因子β（TGF β）途径被强烈激活的维甲酸治疗的肾母细胞瘤细胞。视黄酸和TGF β途径均介导细胞生长的抑制。这些发现代表了维甲酸治疗肾母细胞瘤的潜在益处的第一个分子证据。
Wilms tumor is one of the most frequent neoplasias in children. Our previous microarray screening in a large series of Wilms tumors revealed several candidate genes that are deregulated in advanced tumors and are part of the retinoic acid signaling pathway. To investigate whether retinoic acid could be employed as a novel therapeutic agent in these tumors, we treated cultured Wilms tumor cells with different concentrations of all-trans retinoic acid (ATRA) and assessed gene expression changes by real-time RT-PCR as well as microarray analysis. Several genes like RARRES1, RARRES3, CTGF, CKS2, CCNA2, IGFBP3, UBE2C, CCL2 or ITM2B that were previously found to be deregulated in advanced tumors exhibited opposite expression changes after ATRA treatment. In addition to enhanced retinoid signaling, the transforming growth factor-beta (TGF beta) pathway was strongly activated by ATRA treatment of Wilms tumor cells. Both the retinoic acid and the TGFbeta pathway mediate inhibition of cell growth. These findings represent the first molecular evidence of a potential benefit from ATRA treatment in Wilms tumors.