Mandal Soma, Curtis Linda, Pind Molly, Murphy Leigh C, Watson Peter H
Department of Pathology, University of Manitoba, Winnipeg, Manitoba, Canada.
Exp Cell Res. 2007 Aug 15;313(14):3016-25. doi: 10.1016/j.yexcr.2007.03.020. Epub 2007 Mar 30.
S100A7 (psoriasin) is highly expressed in preinvasive breast carcinomas and in a subset of poor prognosis invasive tumors. To determine the influence of S100A7 expression on ERalpha negative breast cancer, we profiled mRNA gene expression by Microarray and SAGE analysis, using the ERalpha negative MDA-MB-231 cell line model. Statistically significant transcripts of genes with very high differential expression were further validated by QPCR in both MDA-MB-231 and MDA-MB-468 cell lines expressing exogenous and endogenous S100A7. S100A7 expression correlated with increases in genes associated with MHC class II receptor activity, antigen processing and antigen presentation, and immune cell activation. The transcription factors (TFs) prediction tool CARRIE confirmed an association between TFs reported to be upregulated by S100A7 (NF-kappaB, AP-1, and HIF1) and the regulation of many genes in this dataset. The relationship between S100A7 up-regulation and the MHC class II and HLA-class II molecule coding gene CD74 was examined further in a cohort of ERalpha negative breast tumors by tissue microarray (TMA) and immunohistochemistry (IHC), confirming a significant association in vivo (p=0.042, n=149). These results are consistent with a role for S100A7 in modulating the immune response which may be a factor in early breast tumor progression.
S100A7（牛皮癣素）在侵袭前乳腺癌以及一部分预后较差的侵袭性肿瘤中高表达。为了确定S100A7表达对雌激素受体α（ERα）阴性乳腺癌的影响，我们使用ERα阴性的MDA-MB-231细胞系模型，通过微阵列和基因表达序列分析（SAGE）对mRNA基因表达进行了分析。在表达外源性和内源性S100A7的MDA-MB-231和MDA-MB-468细胞系中，通过定量聚合酶链反应（QPCR）进一步验证了差异表达非常高的基因的具有统计学意义的转录本。S100A7表达与与MHC II类受体活性、抗原加工和抗原呈递以及免疫细胞激活相关的基因增加相关。转录因子（TF）预测工具CARRIE证实了据报道被S100A7上调的TF（核因子κB、激活蛋白-1和缺氧诱导因子1）与该数据集中许多基因的调控之间的关联。通过组织微阵列（TMA）和免疫组织化学（IHC）在一组ERα阴性乳腺肿瘤中进一步研究了S100A7上调与MHC II类和HLA-II类分子编码基因CD74之间的关系，证实了体内存在显著关联（p = 0.042，n = 149）。这些结果与S100A7在调节免疫反应中发挥作用一致，这可能是早期乳腺肿瘤进展的一个因素。
