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 ␦ (C/EBP␦, CEBPD) is induced by tumor necrosis factor ␣ (TNF␣) and expressed in chronically inflamed tissue. In this study, we show that TNF␣ promotes aneuploidy. Loss of CEBPD attenuated TNF␣-induced aneuploidy, and CEBPD caused centromere abnormality. Additionally, TNF␣-induced CEBPD expression augmented anchorage-independent growth. We found that TNF␣ 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.
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