中文摘要：

目的 采用基因芯片技术检测乳腺癌MCF-7细胞系他莫昔芬（Tamoxifen,TAM）耐受的差异表达基因,探讨S100p对MCF-7细胞TAM耐受和细胞迁移能力的影响。方法 提取MCF-7和耐药型MCF-7（简称MCF-7R）细胞系总RNA,应用安捷伦（Agilent）基因芯片检测二者差异表达基因。随机选取差异表达基因,应用实时定量PCR（qRT-PCR）技术验证;基因干扰技术下调MCF-7R细胞系S100p的表达,研究S100p对细胞耐药与迁移能力的影响;生存曲线（KM plot）分析过表达S100p与乳腺癌患者无复发生存率（relapse free survival,RFS）及无远处转移生存率（distant metastasis free survival,DMFS）的相关性。结果 检测出显著差异基因4 108个,与MCF-7细胞系相比,MCF-7R上调表达1 983个,下调2 025个。S100钙结合蛋白家族基因多个成员均有显著差异表达;与MCF-7相比,MCF-7R细胞系中S100p mRNA和蛋白表达显著上调,干扰其蛋白表达后,MCF-7R TAM耐受性明显降低（P〈0.01）,细胞迁移能力显著减弱（P〈0.01）;KM plot分析与低表达S100p乳腺癌患者比较,高表达患者RFS（P〈0.01）及DMSF（P=0.01）均显著降低。结论 S100p能够促进乳腺癌细胞TAM耐受和增强细胞迁移能力。

英文摘要：

Objective To investigate the differential gene expression patterns in human breast cancer MCF-7 cells during the development of tamoxifen （TAM） resistance with cDNA microarray, and determine the effect of SlOOp on TAM resistance and migration. Methods Total RNA was extracted from tamoxifen- sensitive MCF-7 cell line and its resistance cell line MCF-7-TAM resistance （MCF-7R）. The probes were hybridized with Agilent gene chips and the fluorescence images of the chips were obtained with Agilent Microarray Scanner. The microarray results were confirmed by real-time quantitative PCR （qRT-PCR） via selecting genes randomly. S100p was down-regulated by siRNA to determine the influence on TAM resistance and migration. Survival analysis was carried out to evaluate clinical relevance of S100p on relapse free survival or distant metastasis free survival by Kaplan-Meier plot. Results Of the 4 108 genes with altered expression, there were 1 983 up-regulated genes and 2 025 down-regulated genes in MCF-7R cells compared with MCF-7 cells. The expression levels of many S100 family members were differentially regulated. The expression levels of S100p mRNA and protein were obviously up-regulated in MCF-7R cells, and after RNA interference, MCF-7R cells showed significantly decreased migration and reduced TAM resistance （ P 〈 0.01 ）. Kaplan-Meier plot indicated that the patients with higher-expressed SlOOp had lower relapse free survival （ RFS, P 〈 0.01 ） and distant metastasis free survival （ DMSF, P = 0.01 ） compared with the low-expressed patients （ P 〈 0. 01 ）. Conclusion SlOOp promotes TAM resistance and migration capacity in breast cancer cells.