Differential expression of Bcl-2 and Bax may enhance neuroblastoma survival
Differential expression of Bcl-2 and Bax may enhance neuroblastoma survival
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DOI：
10.1053/jpsu.2003.50085
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发表时间：
2003-03-01
影响因子：
2.4
通讯作者：
Chen, MK
中科院分区：
文献类型：
--
作者：
Beierle, EA;Dai, W;Chen, MK
背景/目的：侵袭性肿瘤可能通过改变Bcl-2蛋白的表达来减少细胞凋亡，提高生存率。作者先前报道了当神经母细胞瘤细胞与肝细胞共培养以刺激转移环境时，细胞凋亡减少。我们推测，在转移性神经母细胞瘤细胞培养模型中生长的神经母细胞瘤细胞中，促凋亡（Bax）和促存活（Bcl-2和Mcl-1）蛋白的表达会发生改变。方法：将人神经母细胞瘤细胞（IMR-32）单独培养或与人肝细胞共培养2、3或4天。逆转录聚合酶链式反应（RT-PCR）检测Bcl-2、Mcl-1和Bax mRNA。结果：在共培养的神经母细胞瘤细胞中，抗凋亡蛋白Bcl-2在第4天显著升高。促凋亡蛋白Bax在第3天显著减少。Mcl-1在本研究中未发生明显变化。结论：当神经母细胞瘤细胞置于共培养中时，促存活蛋白Bcl-2上调，而促凋亡蛋白Bax下调。这些变化的结合可以最大限度地提高神经母细胞瘤细胞共培养的存活率。神经母细胞瘤转移或消退的倾向可能与其调节Bcl-2蛋白家族不同成员表达的差异能力有关。版权所有，爱思唯尔科学（美国）。版权所有。
Background/Purpose: Aggressive tumors may alter their expression of Bcl-2 proteins to decrease apoptosis and increase survival. The authors reported previously that neuroblastoma cells have diminished apoptosis when placed in coculture with hepatocytes to stimulate a metastatic environment. It was hypothesized that the expression of proapoptotic (Bax) and prosurvival (Bcl-2 and Mcl-1) proteins would be altered in neuroblastoma cells grown in a cell culture model of metastatic neuroblastoma.Methods: Human neuroblastoma cells (IMR-32) were grown alone or in coculture with human hepatocytes for 2, 3, or 4 days. Bcl-2, Mcl-1, and Bax mRNA were measured with reverse transcriptase polymerase chain reaction (RT-PCR).Results: Bcl-2, an antiapoptotic protein, was significantly increased in cocultured neuroblastoma cells by day 4. Bax, a aproapoptotic protein, was significantly diminished by day 3. No significant change in Mcl-1 occurred in this study.Conclusions: When neuroblastoma cells placed in coculture, the prosurvival protein, Bcl-2, is upregulated whereas the proapoptotic protein, Bax, is downregulated. The combination of these changes can maximally enhance the survival rate of neuroblastoma cells in coculture. The propensity for neuroblastoma to either metastasize or regress may be associated with its ability to differentially regulate the expression of different members of the Bcl-2 protein family. Copyright 2003, Elsevier Science (USA). All rights reserved.