title: Insulin upregulates the expression of zinc finger and BTB domain-containing             7A in HepG2 cells.
abstract: Zinc finger and BTB domain-containing 7A (Zbtb7A) is a proto-oncogene overexpressed in numerous cancers. In this study, we explored the mechanism of insulin-induced Zbtb7A expression. Real-time PCR and western blotting were used to detect Zbtb7A expression. Zbtb7A promoter activity was monitored by Luciferase reporter assay. It was shown that insulin elevates the mRNA and protein levels of the Zbtb7A gene in HepG2 cells. Using chemical inhibitors of insulin downstream pathways, we demonstrated that the insulin-induced Zbtb7A gene expression was completely blocked by LY294002, a PI3K/AKT inhibitor, and partially attenuated by the MAPK inhibitor PD98059. Transfection of HepG2 cells with a 1 kb Zbtb7A promoter-luciferase reporter construct revealed a dose-dependent activation of the Zbtb7A promoter by insulin, while mutation of the Sp1 binding site within the Zbtb7A promoter resulted in the failure of insulin-induced promoter activation, suggesting that insulin increases Zbtb7A expression through transcriptional regulation mediated by Sp1 in HepG2 cells.
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing 100084,                     P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Tian
authors.forename: Yuyang
authors.initials: Y
authors.lastname: Jiang
mesh_terms: D001665:Binding Sites; D002867:Chromones / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology; D056945:Hep G2 Cells; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011401:Promoter Regions, Genetic; D000090063:Proto-Oncogene Mas; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D016329:Sp1 Transcription Factor / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D002867:Chromones; D004268:DNA-Binding Proteins; D005419:Flavonoids; D007328:Insulin; D020928:Mitogen-Activated Protein Kinases; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D000090063:Proto-Oncogene Mas; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger; D016329:Sp1 Transcription Factor; D014157:Transcription Factors; C000715470:MAS1 protein, human; C485514:ZBTB7A protein, human; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one