Trev and Joyce Deeley Research Centre, British Columbia Cancer Agency, Victoria, British Columbia, Canada.
Oncogene. 2010 Apr 8;29(14):2083-92. doi: 10.1038/onc.2009.488. Epub 2010 Jan 18.
S100A7 promotes aggressive features in breast cancer, although regulation of its expression is poorly understood. As S100A7 associates with inflammation in skin and breast tissue, we hypothesized that inflammatory cytokines may regulate S100A7 in breast cancer. We therefore examined the effects of several cytokines, among which oncostatin-M (OSM) and the related cytokine, interleukin (IL)-6, showed the most significant effects on S100A7 expression in breast tumor cells in vitro. Both cytokines consistently induced S100A7 expression in three cell lines (MCF7, T47D and MDA-MB-468) in a dose- and time-dependent manner. Induction of S100A7 was inhibited by blockade of STAT3, phosphatidylinositol 3 kinase (PI3K) and ERK1/2 signaling and small interference RNA (siRNA)-mediated knockdown of S100A7 eliminated the promigratory effects of OSM treatment. S100A7 mRNA levels in a case-control cohort of breast tumors (n=20) were significantly associated with expression of the OSM receptor beta (OSMRbeta) chain (P=0.0098). This association was confirmed using publicly available microarray data from an independent breast tumor cohort (n=201, P=0.0005) and a correlation between S100A7 and poor patient survival was observed specifically in cases with high OSMRbeta expression (HR=2.35; P=0.0396; n=85). We conclude that inflammatory cytokines can regulate S100A7 expression and that S100A7 may mediate some of their effects in breast cancer.
S100A7 促进乳腺癌的侵袭性特征，但其表达的调节机制尚不清楚。由于 S100A7 与皮肤和乳腺组织的炎症有关，我们假设炎症细胞因子可能调节乳腺癌中的 S100A7。因此，我们研究了几种细胞因子的作用，其中，oncostatin-M (OSM) 和相关细胞因子白细胞介素 (IL)-6 对乳腺癌肿瘤细胞中 S100A7 的表达有最显著的影响。这两种细胞因子在三种细胞系（MCF7、T47D 和 MDA-MB-468）中均以剂量和时间依赖的方式一致诱导 S100A7 的表达。STAT3、磷脂酰肌醇 3 激酶 (PI3K) 和 ERK1/2 信号通路的阻断以及 S100A7 的小干扰 RNA (siRNA) 介导的敲低抑制了 S100A7 的诱导。在乳腺癌病例对照队列（n=20）中，S100A7 mRNA 水平与 OSM 受体β链（OSMRbeta）的表达显著相关（P=0.0098）。使用来自独立乳腺癌肿瘤队列（n=201，P=0.0005）的公开可用微阵列数据和 S100A7 与不良患者生存之间的相关性，证实了这一关联，并且在 OSMRbeta 表达较高的病例中观察到 S100A7 与较差的患者生存之间存在特定相关性（HR=2.35；P=0.0396；n=85）。我们的结论是，炎症细胞因子可以调节 S100A7 的表达，并且 S100A7 可能在乳腺癌中介导它们的一些作用。
