Increased expression of proapoptotic BMCC1, a novel gene with the BNIP2 and Cdc42GAP homology (BCH) domain, is associated with favorable prognosis in human neuroblastomas
Increased expression of proapoptotic BMCC1, a novel gene with the BNIP2 and Cdc42GAP homology (BCH) domain, is associated with favorable prognosis in human neuroblastomas
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DOI：
10.1038/sj.onc.1209225
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发表时间：
2006-03-23
期刊：
影响因子：
8
通讯作者：
Nakagawara, A
中科院分区：
文献类型：
--
作者：
Machida, T;Fujita, T;Nakagawara, A
从原发性神经母细胞瘤（NBL）cDNA文库中获得的基因的差异筛选的有利和不利的子集之间已经确定了一个新的基因BCH基序的分子在羧基末端区域1（BMCC 1）。其350 kDa的蛋白产物在COOH端具有Bcl 2-/腺病毒E1 B 19 kDa相互作用蛋白2（BNIP 2）和Cdc 42 GAP同源结构域，在NH 2端附近还具有P环和卷曲螺旋区。BMCC 1在人神经系统以及小鼠胚胎的脊髓、脑和背根神经节中都有高水平表达。免疫组化结果显示，MYCN扩增显示，BMCC 1阳性表达于有利的NBL细胞的胞浆中，而不表达于不利的NBL细胞。使用98个原代NBL的定量实时逆转录PCR显示，BMCC 1的高表达是有利NBL的显著指标。在原代培养的新生小鼠上级颈神经节（SCG）神经元中，mBMCC 1表达在神经生长因子（NGF）诱导分化后下调，在NGF耗竭诱导凋亡过程中上调。此外，BMCC 1的促凋亡功能也建议增加表达的CHP 134 NBL细胞凋亡后，用视黄酸处理，并通过增强的细胞凋亡后，消耗神经生长因子的SCG神经元获得的新生小鼠转基因BMCC 1在原代培养。因此，BMCC 1是NBL预后因子的新成员，可能在调节肿瘤细胞的分化、存活和侵袭性方面发挥重要作用。
Differential screening of the genes obtained from cDNA libraries of primary neuroblastomas ( NBLs) between the favorable and unfavorable subsets has identified a novel gene BCH motif-containing molecule at the carboxyl terminal region 1 (BMCC1). Its 350 kDa protein product possessed a Bcl2-/adenovirus E1B nineteen kDa-interacting protein 2 (BNIP2) and Cdc42GAP homology domain in the COOH-terminus in addition to P-loop and a coiled-coil region near the NH2-terminus. High levels of BMCC1 expression were detected in the human nervous system as well as spinal cord, brain and dorsal root ganglion in mouse embryo. The immunohistochemical study revealed that BMCC1 was positively stained in the cytoplasm of favorable NBL cells but not in unfavorable ones with MYCN amplification. The quantitative real-time reverse transcription-PCR using 98 primary NBLs showed that high expression of BMCC1 was a significant indicator of favorable NBL. In primary culture of newborn mice superior cervical ganglion ( SCG) neurons, mBMCC1 expression was downregulated after nerve growth factor (NGF)-induced differentiation, and upregulated during the NGF-depletion-induced apoptosis. Furthermore, the proapoptotic function of BMCC1 was also suggested by increased expression in CHP134 NBL cells undergoing apoptosis after treatment with retinoic acid, and by an enhanced apoptosis after depletion of NGF in the SCG neurons obtained from newborn mice transgenic with BMCC1 in primary culture. Thus, BMCC1 is a new member of prognostic factors for NBL and may play an important role in regulating differentiation, survival and aggressiveness of the tumor cells.