کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6106118 | 1211156 | 2011 | 10 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Research ArticleCharacterization of the transcriptional signature of C/EBPbeta isoforms (LAP/LIP) in Hep3B cells: Implication of LIP in pro-survival functions Research ArticleCharacterization of the transcriptional signature of C/EBPbeta isoforms (LAP/LIP) in Hep3B cells: Implication of LIP in pro-survival functions](/preview/png/6106118.png)
Background & AimsC/EBPbeta is an important mediator of several cellular processes, such as differentiation, proliferation, and survival of hepatic cells. However, a complete catalog of the targets of C/EBPbeta or the mechanism by which this transcription factor regulates certain liver-dependent pathways has not been clearly determined. Two major natural isoforms of this transcription factor exist: the liver-enriched activating protein (LAP) and the liver-enriched inhibitory protein (LIP), a functional LAP antagonist. In this study, we used the opposing transcriptional effects driven by LAP and LIP to determine the genuine C/EBPbeta molecular signature in the Hep3B human hepatoma cell line. We subsequently investigated the role of each of the LAP and LIP isoforms in drug-induced Hep3B cell death.MethodsWe engineered Hep3B cells with regulated LAP or LIP expression using the Tet-off expression system. The genes that showed inverse regulation by LAP and LIP were identified by cDNA array analysis. The cohort of direct-C/EBPbeta-targets was distinguished from indirect-targets by ChIP-on-chip analysis.ResultsWe characterized 676 genes by this approach. Among these genes, 39 are novel direct targets of C/EBPbeta. Eleven of these new direct targets are involved in cell survival, suggesting critical roles for LAP/LIP isoforms in this cellular process. Therefore, we examined the effects of LAP and LIP over-expression on cell survival. We show that LIP promotes survival in staurosporine- or taxol-induced Hep3B cell death.ConclusionsOur study provides new molecular and cellular insights into the role of C/EBPbeta in cells of hepatic origin.
Journal: Journal of Hepatology - Volume 54, Issue 6, June 2011, Pages 1185-1194