Expression profiling of CC531 colon carcinoma cells reveals similar regulation of β-catenin target genes by both butyrate and aspirin
Expression profiling of CC531 colon carcinoma cells reveals similar regulation of β-catenin target genes by both butyrate and aspirin
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DOI：
10.1002/ijc.11215
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发表时间：
2003-08-20
影响因子：
6.4
通讯作者：
Koesters, R
中科院分区：
文献类型：
--
作者：
Germann, A;Dihlmann, S;Koesters, R
CC531细胞系已被广泛用于研究肿瘤生长和转移的不同方面，并为开发新型抗肿瘤策略提供了良好的实验平台。为了在分子水平上表征 CC531 模型，我们筛选了涵盖重要信号转导途径的基因突变，这些信号转导途径已知在结肠癌发生过程中发挥重要作用，即 wnt 和 ki-ras 信号转导途径。我们发现了原型β-连环蛋白（Ctnnbl）突变（Thr（41）IIe）和ki-ras（G12B）突变，为CC531细胞中这些通路的组成型激活提供了明确的证据。我们进一步建立了 CC531 细胞的全面基因表达谱，并研究了丁酸盐和阿司匹林这两种抗肿瘤药物的分子反应。使用寡核苷酸微阵列，我们筛选了 7,700 个基因的表达水平，并鉴定了总共 398 个基因，其表达在丁酸盐处理后发生显着变化。当使用阿司匹林时，121 个基因发生显着改变。有趣的是，有 36 个基因同时受到丁酸和阿司匹林的调节，其中 35 个基因的调节方向相同。我们发现了 7 个差异表达基因：cyclin DI、cyclin E、c-myc、FoslI、c-fos、Cd44 和卵泡抑素，它们是 β-catenin 和/或 ras 途径的已知靶标。在所有情况下，丁酸和阿司匹林逆转了通常在这些致癌途径的活跃信号传导中发现的表达变化。微阵列数据可获取 (http://ncbi.nim.nih.gov/geo/)。 (C) 2003 Wiley-Liss, Inc.
The CC531 cell line has been widely used to study different aspects of tumor growth and metastasis and provides an excellent experimental platform to develop novel antitumor strategies. To characterize the CC531 model at the molecular level, we screened for mutations in genes covering important signal-transduction pathways that are known to play major roles during colon carcinogenesis, the wnt and the ki-ras signaling pathways. We found both a prototypic beta-catenin (Ctnnbl) mutation (Thr(41)IIe) and a ki-ras (G12B) mutation, providing unambiguous evidence for the constitutive activation of these pathways in CC531 cells. We further established comprehensive gene expression profiles of CC531 cells and investigated the molecular response to 2 antitumor drugs, butyrate and aspirin. Using oligonucleotide microarrays, we screened the expression levels of 7,700 genes and identified a total of 398 genes whose expression was significantly changed upon treatment with butyrate. When using aspirin, 121 genes were significantly altered. Interestingly, 36 genes were regulated by both butyrate and aspirin and 35 of them were regulated in the same direction. We found 7 differentially expressed genes, cyclin DI, cyclin E, c-myc, FoslI, c-fos, Cd44 and follistatin, which are known targets of the beta-catenin and/or the ras pathway. In all cases, butyrate and aspirin reversed the changes in expression normally found in response to active signaling of these oncogenic pathways. The microarray data are available (http://ncbi. nim.nih.gov/geo/). (C) 2003 Wiley-Liss, Inc.