Activator protein 2 alpha (AP2α) suppresses 42 kDa C/CAAT enhancer binding protein α (p42 cEBPα) in head and neck squamous cell carcinoma

Abstract

The tumor suppressor C/CAAT enhancer binding protein alpha (CIEBPα) is a transcription factor involved in cell cycle control and cellular differentiation. A recent study showed that CIEBPα 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/EBPα 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 AP2α binding sites. AP2α suppresses C/ EBPα promoter activity and protein expression. Interestingly, silencing ,4P2α bv shRNA increases the antiproliferative isoform of C/EBPα (p42 C/EBPα). Furthermore, growth analysis revealed that these 2 isoforms yield very different proliferative properties in HNSCC. © 2008 Wiley-Liss, Inc.