Activator protein 2 alpha (AP2alpha) suppresses 42 kDa C/CAAT enhancer binding protein alpha (p42(C/EBPalpha)) in head and neck squamous cell carcinoma.
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.
Bennett
Kristi L
KL
Department of Molecular Genetics, Division of Human Cancer Genetics, The Ohio State University, Columbus, OH, USA.
Romigh
Todd
T
Arab
Khelifa
K
Teresi
Rosemary E
RE
Tada
Yasuhiro
Y
Eng
Charis
C
Plass
Christoph
C
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
D022763:CCAAT-Enhancer-Binding Protein-alpha; D022762:CCAAT-Enhancer-Binding Proteins; C515848:CEBPA protein, human; D017931:DNA Primers; D018076:DNA, Complementary; D012334:RNA, Neoplasm