Effect of Benzo[a]pyrene Diol Epoxide on Expression of Retinoic Acid Receptor-β in Immortalized Esophageal Epithelial Cells and Esophageal Cancer Cells

2001 ◽  
Vol 281 (4) ◽  
pp. 872-877 ◽  
Author(s):  
Shumei Song ◽  
Xiao-Chun Xu
Oncogene ◽  
2002 ◽  
Vol 21 (3) ◽  
pp. 411-418 ◽  
Author(s):  
Ming Li ◽  
Shumei Song ◽  
Scott M Lippman ◽  
Xiao-kun Zhang ◽  
Xiaoming Liu ◽  
...  

1995 ◽  
Vol 109 (1) ◽  
pp. 77-86 ◽  
Author(s):  
Bas-jan M. van der Leede ◽  
Gert E. Folkers ◽  
Christina E. van den Brink ◽  
Paul T. van der Saag ◽  
Bart van der Burg

2000 ◽  
Vol 20 (3) ◽  
pp. 957-970 ◽  
Author(s):  
Bingzhen Lin ◽  
Guo-quan Chen ◽  
Dongmei Xiao ◽  
Siva Kumar Kolluri ◽  
Xihua Cao ◽  
...  

ABSTRACT Retinoic acid receptor β (RARβ) plays a critical role in mediating the anticancer effects of retinoids. Expression of RARβ is highly induced by retinoic acid (RA) through a RA response element (βRARE) that is activated by heterodimers of RARs and retinoid X receptors (RXRs). However, RARβ induction is often lost in cancer cells despite expression of RARs and RXRs. In this study, we provide evidence that orphan receptor COUP-TF is required for induction of RARβ expression, growth inhibition, and apoptosis by RA in cancer cells. Expression of COUP-TF correlates with RARβ induction in a variety of cancer cell lines. In addition, stable expression of COUP-TF in COUP-TF-negative cancer cells restores induction of RARβ expression, growth inhibition, and apoptosis by RA, whereas inhibition of COUP-TF by expression of COUP-TF antisense RNA represses the RA effects. In a transient transfection assay, COUP-TF strongly induced transcriptional activity of the RARβ promoter in a RA- and RARα-dependent manner. By mutation analysis, we demonstrate that the effect of COUP-TF requires its binding to a DR-8 element present in the RARβ promoter. The binding of COUP-TF to the DR-8 element synergistically increases the RA-dependent RARα transactivation function by enhancing the interaction of RARα with its coactivator CREB binding protein. These results demonstrate that COUP-TF, by serving as an accessory protein for RARα to induce RARβ expression, plays a critical role in regulating the anticancer activities of retinoids.


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