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Zusammenfassung: <jats:title>Abstract</jats:title><jats:p>The tumor suppressor <jats:italic>C/CAAT</jats:italic> enhancer binding protein alpha (<jats:italic>C/EBP</jats:italic>α) is a transcription factor involved in cell cycle control and cellular differentiation. A recent study showed that <jats:italic>C/EBP</jats:italic>α 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 <jats:italic>C/EBP</jats:italic>α 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 <jats:italic>C/EBP</jats:italic>α promoter activity and protein expression. Interestingly, silencing AP2α by shRNA increases the antiproliferative isoform of <jats:italic>C/EBP</jats:italic>α (p42<jats:sup>C/EBPα</jats:sup>). Furthermore, growth analysis revealed that these 2 isoforms yield very different proliferative properties in HNSCC. © 2008 Wiley‐Liss, Inc.</jats:p>
Umfang: 1285-1292
ISSN: 0020-7136
1097-0215
DOI: 10.1002/ijc.24087