title: CCAAT/enhancer-binding protein delta mediates tumor necrosis factor alpha-induced Aurora kinase C transcription and promotes genomic instability.
abstract: Epidemiologic and clinical research indicates that chronic inflammation increases the risk of certain cancers, possibly through chromosomal instability. However, the mechanism of inflammation-dependent chromosomal instability associated with tumorigenesis is not well characterized. The transcription factor CCAAT/enhancer-binding protein δ (C/EBPδ, CEBPD) is induced by tumor necrosis factor α (TNFα) and expressed in chronically inflamed tissue. In this study, we show that TNFα promotes aneuploidy. Loss of CEBPD attenuated TNFα-induced aneuploidy, and CEBPD caused centromere abnormality. Additionally, TNFα-induced CEBPD expression augmented anchorage-independent growth. We found that TNFα induced expression of aurora kinase C (AURKC) through CEBPD, and that AURKC also causes aneuploidy. Furthermore, high CEBPD expression correlated with AURKC expression in inflamed cervical tissue specimens. These data provide insight into a novel function for CEBPD in inducing genomic instability through the activation of AURKC expression in response to inflammatory signals.
authors.affiliation: Institute of Bioinformatics and Biosignal Transduction, College of Bioscience and Biotechnology, Tainan 701, Taiwan, Republic of China.
authors.forename: Sin-Rong
authors.initials: SR
authors.lastname: Wu
authors.affiliation: Department of Pathology, Chi-Mei Medical Center, Tainan 710, Taiwan, Republic of China.
authors.forename: Chien-Feng
authors.initials: CF
authors.lastname: Li
authors.affiliation: Institute of Bioinformatics and Biosignal Transduction, College of Bioscience and Biotechnology, Tainan 701, Taiwan, Republic of China; Molecular Inflammation Research Center, College of Bioscience and Biotechnology, Tainan 701, Taiwan, Republic of China; Infectious Disease and Signaling Research Center, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan, Republic of China.
authors.forename: Liang-Yi
authors.initials: LY
authors.lastname: Hung
authors.affiliation: Department of Medicine, Graduate Institute of Biochemistry, Kaohsiung Medical University, Kaohsiung 807, Taiwan, Republic of China.
authors.forename: A-Mei
authors.initials: AM
authors.lastname: Huang
authors.affiliation: Institute of Bioinformatics and Biosignal Transduction, College of Bioscience and Biotechnology, Tainan 701, Taiwan, Republic of China; Molecular Inflammation Research Center, College of Bioscience and Biotechnology, Tainan 701, Taiwan, Republic of China; Infectious Disease and Signaling Research Center, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan, Republic of China.
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Tseng
authors.affiliation: Institute of Bioinformatics and Biosignal Transduction, College of Bioscience and Biotechnology, Tainan 701, Taiwan, Republic of China.
authors.forename: Jen-Hui
authors.initials: JH
authors.lastname: Tsou
authors.affiliation: Institute of Bioinformatics and Biosignal Transduction, College of Bioscience and Biotechnology, Tainan 701, Taiwan, Republic of China; Molecular Inflammation Research Center, College of Bioscience and Biotechnology, Tainan 701, Taiwan, Republic of China; Infectious Disease and Signaling Research Center, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan, Republic of China; Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan, Republic of China. Electronic address: wwwjm4721@yahoo.com.tw.
authors.forename: Ju-Ming
authors.initials: JM
authors.lastname: Wang
mesh_terms: D000782:Aneuploidy; D000818:Animals; D064108:Aurora Kinase C; D064127:Aurora Kinases; D051743:CCAAT-Enhancer-Binding Protein-delta / Q000235:genetics / Q000378:metabolism*; D002503:Centromere / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002584:Cervix Uteri / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000235:genetics; D042822:Genomic Instability; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis* / Q000235:genetics; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000494:pharmacology; D002575:Uterine Cervicitis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: C497252:CEBPD protein, human; C497253:Cebpd protein, mouse; D014409:Tumor Necrosis Factor-alpha; D051743:CCAAT-Enhancer-Binding Protein-delta; C576927:AURKC protein, human; C576928:Aurkc protein, mouse; D064108:Aurora Kinase C; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases