Carlsson H, Petersson S, Enerbäck C
Department of Clinical Genetics, Sahlgrenska University Hospital, SE-416 85 Göteborg, Sweden.
Int J Oncol. 2005 Dec;27(6):1473-81.
Gene expression patterns in ductal carcinoma in situ (DCIS) and invasive and metastatic breast tumors have been determined using serial analysis of gene expression (SAGE). The purpose of this approach was to identify biologically and clinically meaningful subgroups of DCIS with a high risk of progression to invasive disease. The analyses have led to the identification of several differentially expressed genes, such as HIN-1, dermcidin and S100A7 (psoriasin). The aim of the present study was further to delineate the expression profile of S100 genes using information from 22 breast epithelial SAGE libraries. We demonstrated the down-regulation of S100A6 and S100A10 in breast cancer, irrespective of pathological stage. S100P and S100Z were both up-regulated in cancer; whereas S100A7, S100A8 and S100A9 were strongly up-regulated only in DCIS. The hierarchical clustering of S100 gene expression in these 22 libraries revealed two major groups with distinguishable S100 gene expression profiles. One of them was characterized by the high concomitant expression of S100A7, S100A8 and S100A9. Using SAGE informatics, we found 21 genes with a high positive correlation to S100A7 expression in libraries representing different categories of tissues archived at SAGE Genie, suggesting a function of psoriasin that is not tissue specific. Like S100A7, several of these genes displayed cation-binding properties. We also report the strong correlation in the breast epithelial SAGE libraries between the expression of S100A7 and genes reported as being up-regulated in DCIS, as well as in the inflammatory skin disorder, psoriasis; including RGS5, UPK1A, TMPRSS3, S100A9, p53, SCCA1, SCCA2 and KRT17.
已通过基因表达序列分析（SAGE）确定了导管原位癌（DCIS）以及侵袭性和转移性乳腺肿瘤中的基因表达模式。该方法的目的是识别具有进展为浸润性疾病高风险的DCIS生物学和临床意义上的亚组。这些分析已导致鉴定出几个差异表达基因，例如HIN-1、皮肤杀菌素和S100A7（牛皮癣素）。本研究的目的是进一步利用来自22个乳腺上皮SAGE文库的信息描绘S100基因的表达谱。我们证明了乳腺癌中S100A6和S100A10的下调，与病理分期无关。S100P和S100Z在癌症中均上调；而S100A7、S100A8和S100A9仅在DCIS中强烈上调。这22个文库中S100基因表达的层次聚类揭示了具有可区分S100基因表达谱的两个主要组。其中一组的特征是S100A7、S100A8和S100A9的高伴随表达。利用SAGE信息学，我们在代表保存在SAGE Genie的不同组织类别的文库中发现了21个与S100A7表达高度正相关的基因，提示牛皮癣素具有非组织特异性的功能。与S100A7一样，这些基因中的几个显示出阳离子结合特性。我们还报告了乳腺上皮SAGE文库中S100A7的表达与在DCIS以及炎症性皮肤病牛皮癣中报告上调的基因之间的强相关性；包括RGS5、UPK1A、TMPRSS3、S100A9、p53、SCCA1、SCCA2和KRT17。
