title: SP1 and USF differentially regulate ADAMTS1 gene expression under normoxic and hypoxic conditions in hepatoma cells.
abstract: ADAM metallopeptidase with thrombospondin type I motif, 1 (ADAMTS1) that has both antiangiogenic and aggrecanase activity was dysregulated in many pathophysiologic circumstances. However, there is limited information available on the transcriptional regulation of ADAMTS1 gene. Therefore, this study mainly aimed to identify regulatory regions important for the regulation of ADAMTS1 gene under normoxic and hypoxic conditions in human hepatoma cells (HEP3B). Cultured HEP3B cells were exposed to normal oxygen condition, and Cobalt chloride (CoCl2) induced the hypoxic condition, which is an HIF-1 inducer. The cocl2-induced hypoxic condition led to the induced ADAMTS1 mRNA and protein expression in Hepatoma cells. Differential regulation of SP1 and USF transcription factors on ADAMTS1 gene expression was determined by transcriptional activity, mRNA and protein level of ADAMTS1 gene. Ectopic expression of SP1 and USF transcription factors resulted in the decrease in ADAMTS1 transcriptional activity of all promoter constructs consistent with mRNA and protein level in normoxic condition. However, overexpression of SP1 and USF led to the increase of ADAMTS1 gene expressions at mRNA and protein level in hypoxic condition. On the other hand, C/EBPα transcription factor didn't show any statistically significant effect on ADAMTS1 gene expression at mRNA, protein and transcriptional level under normoxic and hypoxic condition.
authors: Department of Molecular Biology and Genetics, Faculty of Art and Science, Balikesir University, 10145 Balikesir, Turkey.
authors: Sumeyye Aydogan
authors: SA
authors: Turkoglu
authors: Department of Molecular Biology and Genetics, Faculty of Art and Science, Balikesir University, 10145 Balikesir, Turkey. Electronic address: fkockar@balikesir.edu.tr.
authors: Feray
authors: F
authors: Kockar
mesh_terms: D051722:ADAM Proteins / Q000096:biosynthesis*; D000071097:ADAMTS1 Protein; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015687:Cell Hypoxia / Q000235:genetics; D045744:Cell Line, Tumor; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D051720:Upstream Stimulatory Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; C515848:CEBPA protein, human; D009363:Neoplasm Proteins; D016329:Sp1 Transcription Factor; C108209:SP1 protein, human; D051720:Upstream Stimulatory Factors; D051722:ADAM Proteins; D000071097:ADAMTS1 Protein; C103859:ADAMTS1 protein, human
keywords: C/EBPα; Hypoxia; Normoxia; SP1; USF; sADAMTS1