ARID3B induces malignant transformation of mouse embryonic fibroblasts and is strongly associated with malignant neuroblastoma
ARID3B induces malignant transformation of mouse embryonic fibroblasts and is strongly associated with malignant neuroblastoma
复制标题
DOI：
10.1158/0008-5472.can-06-0756
复制
发表时间：
2006-09-01
期刊：
影响因子：
11.2
通讯作者：
Nishikawa, Shin-Ichi
中科院分区：
文献类型：
--
作者：
Kobayashi, Kenichiro;Era, Takumi;Nishikawa, Shin-Ichi
ARID3B 是富含 AT 相互作用域 (ARID) 蛋白家族的成员，在胚胎发生过程中神经嵴的存活中发挥着重要作用。在这里，我们报告了 ARID3B 参与恶性神经母细胞瘤（一种源自神经嵴的儿童肿瘤）发展的证据。 (a) ARID3B 由我们测试的所有五种源自神经母细胞瘤的细胞系表达。 (b) 对新鲜神经母细胞瘤肿瘤已发表的 DNA 微阵列数据的分析表明，ARID3B 在 80% 的 IV 期肿瘤中表达，而仅在 9% 的 I-III+IV 期肿瘤中表达。 (c) 反义和 siRNA 处理显着抑制了几种神经母细胞瘤细胞系的体外生长。 (d)通过转染SY5Y神经母细胞瘤细胞系而增加ARID3B表达水平增强了nu/nu小鼠肿瘤生长测定中的恶性程度。 (e) ARID3B 本身可以在体外使小鼠胚胎成纤维细胞 (MEF) 永生化，并且当与 MYCN（神经母细胞瘤的最佳特征癌基因）一起转染时，使 MEF 恶性。因此，ARID3B似乎在神经母细胞瘤的恶性转化中发挥着关键作用，不仅可以作为恶性肿瘤的标志物，而且可以作为目前尚无有效治疗方法的IV期神经母细胞瘤的癌症治疗的潜在靶点。
ARID3B, a member of the AT-rich interaction domain (ARID) family of proteins, plays an essential role in the survival of neural crest during embryogenesis. Here, we report evidence that ARID3B is involved in the development of malignant neuroblastoma, a childhood tumor derived from neural crest. (a) ARID3B is expressed by all five cell lines derived from neuroblastoma tested by us. (b) Analysis of published DNA microarray data of fresh neuroblastoma tumors showed that ARID3B is expressed in 80% of stage IV tumors, whereas only in 9% of stage I-III+IVs tumors. (c) In vitro growth of several neuroblastoma cell lines is suppressed significantly by antisense as well as siRNA treatment. (d) An increase of the ARID3B expression level by transfection in the SY5Y neuroblastoma cell line enhances the malignancy in tumor growth assays in nu/nu mice. (e) ARID3B by itself can immortalize mouse embryonic fibroblasts (MEFs) in vitro and confers malignancy to MEF when transfected together with MYCN, the best characterized oncogene for neuroblastoma. Thus, ARID3B seems to play a key role in the malignant transformation of neuroblastoma and may serve not only as a marker of malignancy but also as a potential target for cancer therapy of stage IV neuroblastoma for which there is currently no effective treatment available.