Mechanisms of confluence-dependent expression of CD26 in colon cancer cell lines.
Mechanisms of confluence-dependent expression of CD26 in colon cancer cell lines.
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DOI：
10.1186/1471-2407-11-51
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发表时间：
2011-02-01
期刊：
影响因子：
3.8
通讯作者：
Dang NH
中科院分区：
文献类型：
--
作者：
Abe M;Havre PA;Urasaki Y;Ohnuma K;Morimoto C;Dang LH;Dang NH
CD26（二肽基肽酶IV， DPPIV）是一种110 kDa的表面糖蛋白，在大多数正常组织中表达，是一种潜在的治疗癌症的新靶点。我们的工作评估了结肠癌中融合依赖性CD26表达的机制。将结肠腺癌细胞培养至合流状态，通过免疫荧光和Western blotting检测CD26及其调控相关转录因子的表达。Real-time PCR还用于评估CD26在转录水平上的上调。在短暂转染c-Myc表达质粒和c-Myc特异性siRNA后，进一步评估了c-Myc在不同生长条件下对CD26表达的影响。我们发现结肠癌细胞系HCT-116和HCT-15表现出CD26 mRNA和蛋白的融合依赖性增加，与c-Myc表达降低、USF-1和cdx2水平升高以及HNF-1α表达不变相关。同时，c-Myc在两种细胞系中的异位表达导致CD26表达降低。相反，转染靶向Cdx2的siRNA导致CD26水平降低。重要的是，在无血清培养基中培养细胞，而不是在酸性条件下，会上调CD26。当细胞在无血清培养基中培养时，HIF-1α水平也升高，但它的表达是必需的，但不足以使CD26上调。在结肠癌细胞系中，CD26 mRNA和蛋白水平以融合依赖的方式增加，其中c-Myc作为抑制因子，Cdx2作为CD26表达的增强因子。血清缺失培养基中CD26表达的增强和对HIF-1α的需求提示营养物质或生长因子在调节CD26蛋白表达中的作用。
CD26 (dipeptidyl peptidase IV, DPPIV) is a 110 kDa surface glycoprotein expressed in most normal tissues, and is a potential novel therapeutic target for selected cancers. Our work evaluates the mechanism involved in confluence-dependent CD26 expression in colon cancer. Colon adenocarcinoma cells were grown to confluence, and expression of CD26 and transcription factors implicated in its regulation was confirmed by immunofluorescence and Western blotting. Real-time PCR was also performed to evaluate CD26 upregulation at the transcriptional level. The influence of c-Myc on CD26 expression during different growth conditions was further evaluated following transient transfection of a c-Myc-expressing plasmid and a c-Myc specific siRNA. We found that the colon cancer cell lines HCT-116 and HCT-15 exhibited a confluence-dependent increase in CD26 mRNA and protein, associated with decreased expression of c-Myc, increased USF-1 and Cdx 2 levels, and unchanged HNF-1α expression. Meanwhile, ectopic expression of c-Myc in both cell lines led to decreased CD26 expression. In contrast, transfection of a siRNA targeted to Cdx2 resulted in decreased CD26 level. Importantly, culturing of cells in serum-depleted media, but not acidic conditions, upregulated CD26. While HIF-1α level also increased when cells were cultured in serum-depleted media, its expression was required but not sufficient for CD26 upregulation. CD26 mRNA and protein levels increase in a confluence-dependent manner in colon carcinoma cell lines, with c-Myc acting as a repressor and Cdx2 acting as an enhancer of CD26 expression. The enhanced expression of CD26 in serum-depleted media and a requirement for HIF-1α suggest a role for nutrients or growth factors in the regulation of CD26 protein expression.
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影响因子：
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