人神经母细胞瘤系SK—N—SH侧群细胞基因表达的研究

Gene expression profiles in side population cells of neuroblastoma

目的采用全基因组寡核苷酸微阵列芯片，检测神经母细胞瘤SP细胞与非S．P细胞基因表达的差异，从基因层面探讨SP细胞与肿瘤转移相关性的可能分子机制。方法培养人神经母细胞瘤系SK-N-SH，检测条件稳定后以流式细胞仪行SP细胞分选，将分得的SP及非SP细胞采用RNA表达谱芯片分别检测其基因表达情况，筛选出差异表达基因，并加以分析。结果在人类全基因组中，共筛选出差异基因位点53544个，其中表达上调2倍以上的基因有3453个，表达下调2倍以上的基因有1256个。采用Signalinteractionnetwork分析方法对所有表达差异在2倍以上的基因进行互相作用网络分析得到MAPK3／ERKl是差异基因关系网中最关键的基因，其他的还包括MAPKl4／p38a等。结论MAPK信号转导通路关键组分MAPK3／ERKl、MAPKl4／p38a在SP细胞中高表达，可能是SP细胞与肿瘤转移高相关性的关键分子通路。

Objective To investigate the gene expression profiles of side population （SP） cells in human neuroblastoma SK-N-SH cells. Methods After staining the neuroblastoma SK-N-SH cell line with Hoechst 33 342 dye, the SP and nonside population （non-SP） cells were separated using flow cytometric cell sorting. The isolated SP cells from neuroblastoma SK-N-SH cell line presented several stem cell properties. The mRNA expression profiles were measured by Affymetrix GeneChip oligonu- cleotide array. Results Among the 53544 differentially expressed genes, 3453 were significantly up- regulated more than 2 folds in SP cells. Using signal interaction network analysis, we found that MAPK/ERK1 and MAPK14/p38a signaling pathways played the key role in the up-regulation of these genes. Conclusions The expressions of the gene associated with MAPK/ERK1 and MAPK14/p38a signaling pathway are up-regulated in SP cells, which may be responsible for metastasis of human neu- roblastoma.