CCAAT/Enhancer-Binding Protein β (Nuclear Factor for Interleukin 6) Transactivates the HumanMDR1 Gene by Interaction with an Inverted CCAAT Box in Human Cancer Cells

2004 ◽  
Vol 65 (4) ◽  
pp. 906-916 ◽  
Author(s):  
Kevin G. Chen ◽  
Sanja Sale ◽  
Thomas Tan ◽  
Ralph P. Ermoian ◽  
Branimir I. Sikic
Keyword(s):  
Cancer Cells ◽  
Interleukin 6 ◽  
Human Cancer ◽  
Binding Protein ◽  
Nuclear Factor ◽  
Human Cancer Cells ◽  
Enhancer Binding Protein ◽  
Ccaat Enhancer Binding Protein ◽  
Ccaat Box

scholarly journals CCAAT enhancer binding protein β and hepatocyte nuclear factor 3β are necessary and sufficient to mediate dexamethasone-induced up-regulation of alpha2HS-glycoprotein/fetuin-A gene expression

2006 ◽  
Vol 36 (2) ◽  
pp. 261-277 ◽  
Author(s):  
Michael Wöltje ◽  
Beate Tschöke ◽  
Verena von Bülow ◽  
Ralf Westenfeld ◽  
Bernd Denecke ◽  
...  
Keyword(s):  
Serum Protein ◽  
Binding Protein ◽  
Protein A ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Tissue Remodelling ◽  
Mobility Shift ◽  
Fetuin A ◽  
Enhancer Binding Protein ◽  
Ccaat Enhancer Binding Protein

Alpha2HS-glycoprotein/fetuin-A (Ahsg) is a serum protein preventing soft tissue calcification. In trauma and inflammation, Ahsg is down-regulated and therefore considered a negative acute phase protein. Enhancement of Ahsg expression as a protective serum protein is desirable in several diseases including tissue remodelling after trauma and infection, kidney and heart failure, and cancer. Using reporter gene assays in hepatoma cells combined with electrophoretic mobility shift assays we determined that dexamethasone up-regulates hepatic Ahsg. A steroid response unit at position −146/−119 within the mouse Ahsg promoter mediates the glucocorticoid-induced increase of Ahsg mRNA. It binds the hepatocyte nuclear factor 3β and CCAAT enhancer binding protein β (C/EBP-β). The up-regulation is mediated indirectly via glucocorticoid hormone-induced transcriptional up-regulation in C/EBP-β protein. A high degree of sequence identity in mouse, rat and human Ahsg promoters suggests that the promoter is similarly up-regulated by dexamethasone in all three species. Therefore, our findings suggest that glucocorticoids may be used to enhance the level of Ahsg protein circulating in serum.

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