Stimulation of the intestinal Cdx2 homeobox gene by butyrate in colon cancer cells
Stimulation of the intestinal Cdx2 homeobox gene by butyrate in colon cancer cells
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DOI：
10.1136/gut.50.4.525
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发表时间：
2002-04-01
期刊：
影响因子：
24.5
通讯作者：
Freund, JN
中科院分区：
文献类型：
--
作者：
Domon-Dell, C;Wang, Q;Freund, JN
背景资料：由肠Cdx 2同源框基因编码的转录因子和丁酸钠（NaB）（结肠细菌纤维发酵的副产物）处理对结肠癌细胞系产生类似的作用，因为它们都抑制细胞生长并刺激细胞分化和凋亡。目的：研究NaB是否调节结肠癌细胞系中Cdx 2基因的表达。人腺癌细胞系Caco 2和HT 29在存在或不存在NaB的情况下生长。通过逆转录-聚合酶链反应分析细胞Cdx 2 mRNA的表达，通过Western印迹和电迁移率变化分析蛋白质的表达，以及通过转染荧光素酶报告质粒Cdx 2启动子的转录活性。结果：在HT 29和Caco 2细胞中，NaB刺激Cdx 2 mRNA和蛋白质的表达以及Cdx 2启动子的转录活性。NaB对Cdx 2启动子活性的刺激具有剂量和时间依赖性。Cdx 2启动子包含参与或相反地钝化NaB所施加的刺激作用的离散区域。此外，NaB刺激的Cdx 2启动子的转录活性下调致癌ras.Conclusion：这项研究是第一次报告的肠道特异性转录因子，Cdx 2，丁酸刺激。因此，它提供了丁酸盐控制结肠癌细胞增殖和分化的新机制。
Background: The transcription factor encoded by the intestinal Cdx2 homeobox gene and treatment with sodium butyrate (NaB), a byproduct of fibre fermentation by colonic bacteria, exert similar effects on colon cancer cell lines as they both inhibit cell growth and stimulate cell differentiation and apoptosis.Aim: To investigate whether NaB regulates expression of the Cdx2 gene in colon cancer cell lines.Methods: Human adenocarcinoma cell lines Caco2 and HT29 were grown In the presence or absence of NaB. Cells were analysed for Cdx2 mRNA expression by reverse transcription-polymerase chain reaction, for protein expression by western blotting and electromobility shift assays, and for transcriptional activity of the Cdx2 promoter by transfection with luciferase reporter plasmids.Results: In HT29 and Caco2 cells, NaB stimulated Cdx2 mRNA and protein expression as well as transcriptional activity of the Cdx2 promoter. Stimulation of the activity of the Cdx2 promoter by NaB was dose and time dependent. The Cdx2 promoter contains discrete regions that participate in or inversely that blunt the stimulatory effect exerted by NaB. In addition, NaB stimulated the transcriptional activity of the Cdx2 promoter downregulated by oncogenic ras.Conclusion: This study is the first report of an intestine specific transcription factor, Cdx2, stimulated by butyrate. Thus it provides a new mechanism whereby butyrate controls proliferation and differentiation of colon cancer cells.