激活蛋白2α（AP2α）在头颈部鳞状细胞癌中抑制42 kDa C/CAAT增强子结合蛋白α（p42（C/EBPα））。
Activator protein 2 alpha (AP2alpha) suppresses 42 kDa C/CAAT enhancer binding protein alpha (p42(C/EBPalpha)) in head and neck squamous cell carcinoma.
作者信息
Bennett Kristi L, Romigh Todd, Arab Khelifa, Teresi Rosemary E, Tada Yasuhiro, Eng Charis, Plass Christoph
机构信息
Department of Molecular Genetics, Division of Human Cancer Genetics, The Ohio State University, Columbus, OH, USA.
出版信息
Int J Cancer. 2009 Mar 15;124(6):1285-92. doi: 10.1002/ijc.24087.
Abstract
The tumor suppressor C/CAAT enhancer binding protein alpha (C/EBPalpha) is a transcription factor involved in cell cycle control and cellular differentiation. A recent study showed that C/EBPalpha is frequently downregulated in head and neck squamous cell carcinoma (HNSCC) by DNA methylation in an upstream regulatory region. Here, we investigated how DNA methylation in the upstream regulatory region disrupts the transcriptional regulation of C/EBPalpha in HNSCC. The results reveal that aberrant methylation correlates with methyl binding domain protein binding and repressive histone modifications. This methylated region contains previously uninvestigated AP2alpha binding sites. AP2alpha suppresses C/EBPalpha promoter activity and protein expression. Interestingly, silencing AP2alpha by shRNA increases the antiproliferative isoform of C/EBPalpha (p42(C/EBPalpha)). Furthermore, growth analysis revealed that these 2 isoforms yield very different proliferative properties in HNSCC.
摘要
肿瘤抑制因子C/CAAT增强子结合蛋白α（C/EBPα）是一种参与细胞周期调控和细胞分化的转录因子。最近的一项研究表明，在头颈部鳞状细胞癌（HNSCC）中，C/EBPα在上游调控区域常因DNA甲基化而表达下调。在此，我们研究了上游调控区域的DNA甲基化如何破坏HNSCC中C/EBPα的转录调控。结果显示，异常甲基化与甲基结合域蛋白结合及组蛋白抑制性修饰相关。该甲基化区域包含先前未被研究的AP2α结合位点。AP2α抑制C/EBPα启动子活性和蛋白表达。有趣的是，通过短发夹RNA（shRNA）沉默AP2α可增加C/EBPα的抗增殖异构体（p42（C/EBPα））。此外，生长分析表明，这两种异构体在HNSCC中产生非常不同的增殖特性。
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