title: Activator protein 2 alpha (AP2alpha) suppresses 42 kDa C/CAAT enhancer binding protein alpha (p42(C/EBPalpha)) in head and neck squamous cell carcinoma.
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.
authors.affiliation: Department of Molecular Genetics, Division of Human Cancer Genetics, The Ohio State University, Columbus, OH, USA.
authors.forename: Kristi L
authors.initials: KL
authors.lastname: Bennett
authors.forename: Todd
authors.initials: T
authors.lastname: Romigh
authors.forename: Khelifa
authors.initials: K
authors.lastname: Arab
authors.forename: Rosemary E
authors.initials: RE
authors.lastname: Teresi
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Tada
authors.forename: Charis
authors.initials: C
authors.lastname: Eng
authors.forename: Christoph
authors.initials: C
authors.lastname: Plass
mesh_terms: D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics* / Q000378:metabolism; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D002453:Cell Cycle; D002454:Cell Differentiation; D002455:Cell Division; D045744:Cell Line, Tumor; D017931:DNA Primers; D018076:DNA, Complementary / Q000235:genetics; D015536:Down-Regulation; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D006801:Humans; D016297:Mutagenesis, Site-Directed; D010957:Plasmids; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D014176:Protein Biosynthesis; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D014162:Transfection
chemical_list: D022763:CCAAT-Enhancer-Binding Protein-alpha; D022762:CCAAT-Enhancer-Binding Proteins; C515848:CEBPA protein, human; D017931:DNA Primers; D018076:DNA, Complementary; D012334:RNA, Neoplasm