DRR1 is expressed in the developing nervous system and downregulated during neuroblastoma carcinogenesis
DRR1 is expressed in the developing nervous system and downregulated during neuroblastoma carcinogenesis
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DOI：
10.1016/j.bbrc.2010.03.085
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发表时间：
2010-04-09
影响因子：
3.1
通讯作者：
Kadomatsu, Kenji
中科院分区：
文献类型：
--
作者：
Asano, Yoshizumi;Kishida, Satoshi;Kadomatsu, Kenji
在肾细胞癌中下调1（DRR 1）定位于3p2 1 1，并且是候选肿瘤抑制基因。然而，由于生物学作用尚未阐明。DRR 1蛋白在小鼠胚胎发育过程中主要表达于中枢和周围神经系统的轴突投射中，与该表达模式一致，在胚胎第185天的大鼠的原代培养的皮层神经元的神经突中检测到该蛋白质。这些细胞的存活被RNAi诱导的DRR 1表达下调显著抑制。DRR 1在已建立的癌细胞系（包括成神经细胞瘤细胞）中表达差，而在正常细胞中观察到强表达。成神经细胞瘤模型，MYCN转基因小鼠，揭示了DRR1蛋白表达在腹腔神经节出生后2周时，也观察到神经母细胞增生。然而，出生后8周，在起源于神经节的肿瘤中不再有任何DRR 1蛋白的表达。总之，我们的数据表明，DRR 1蛋白在正常细胞中表达，特别是在胚胎发生期间的神经系统中，参与神经元细胞存活，并且在神经母细胞瘤癌变过程中下调。(C)2010 Elsevier Inc保留所有权利。
Down-regulated in renal cell carcinoma 1 (DRR1) is mapped at 3p2 1 1, and is a candidate tumor suppressor gene However, as biological roles have yet to be elucidated Here, we developed polyclonal antibodies against DRR1 protein, and examined its expression during embryogenesis and carcinogenesis The DRR1 protein was preferentially expressed in axonal projections of the central and peripheral nervous system of mice during embryonic days 10 5-16 5 Consistent with this expression pattern, the protein was detected in the neurites of primary cultured cortical neurons of rats at embryonic day 185 Survival of these cells was significantly inhibited by RNAi-induced downregulation of DRR1 expression DRR1 was poorly expressed in established cancer cell lines, including neuroblastoma cells, whereas strong expression was observed in normal cells A neuroblastoma model, MYCN transgenic mice, revealed that DRR1 protein was expressed in the celiac ganglion 2 weeks after birth when neuroblast hyperplasia was also observed. however, there was no longer any expression of DRR1 protein in tumors originating from the ganglion 8 weeks after birth Together, our data indicate that DRR1 protein is expressed in normal cells, particularly in the nervous system during embryogenesis, is involved in neuronal cell survival, and is downregulated during neuroblastoma carcinogenesis. (C) 2010 Elsevier Inc All rights reserved.