Document Detail

Role of COUP-TFI during retinoic acid-induced differentiation of P19 cells to endodermal cells.
MedLine Citation:
PMID:  23018522     Owner:  NLM     Status:  MEDLINE    
Retinoic acid (RA) is a positive regulator of P19 cell differentiation. Silencing of pre-B cell leukemia transcription factors (PBXs) expression in P19 cells (AS cells) results in a failure of these cells to differentiate to endodermal cells upon RA treatment. Chicken Ovalbumin Upstream Promoter Transcription Factor I (COUP-TFI) is an orphan member of the steroid-thyroid hormone superfamily. RA treatment of wild type P19 cells results in a dramatic increase in the expression of COUP-TFI; however, COUP-TFI mRNA levels fail to be elevated upon RA treatment of AS cells indicating that PBX expression is required for elevation in COUP-TFI expression. To study the role of COUP-TFI during RA-dependent differentiation of P19 cells, AS cells that inducibly express various levels of COUP-TFI were prepared. Exogenous expression of COUP-TFI in AS cells, in a dose-dependent fashion, leads to growth inhibition, modest cell cycle disruption, and early apoptosis. Furthermore, AS cells can overcome the blockage in RA-dependent differentiation to endodermal cells when either pharmacological levels of COUP-TFI are expressed or a combination of both the expression of physiological levels of COUP-TFI and RA treatment. Additionally, the mRNA level of several pluripotency associated genes including OCT-4, DAX-1, and SF-1 in the COUP-TFI expressing AS cells are reduced. Moreover, analysis of the expression of primary RA response genes indicates that COUP-TFI is involved in the regulatory modulation of the expression of at least two genes, CYP26A1 and HoxA1. These studies demonstrate that COUP-TFI functions as a physiologically relevant regulator during RA-mediated endodermal differentiation of P19 cells.
Brandy S Pickens; Bryan W Teets; Kenneth J Soprano; Dianne Robert Soprano
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Journal of cellular physiology     Volume:  228     ISSN:  1097-4652     ISO Abbreviation:  J. Cell. Physiol.     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-01-02     Completed Date:  2013-05-22     Revised Date:  2014-04-02    
Medline Journal Info:
Nlm Unique ID:  0050222     Medline TA:  J Cell Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  791-800     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Wiley Periodicals, Inc.
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MeSH Terms
Apoptosis / drug effects,  genetics
COUP Transcription Factor I / genetics*,  metabolism
COUP Transcription Factor II / genetics,  metabolism
Cell Cycle / drug effects,  genetics
Cell Differentiation / drug effects*,  genetics*
Cells, Cultured
Cytochrome P-450 Enzyme System / genetics,  metabolism
DAX-1 Orphan Nuclear Receptor / genetics,  metabolism
Endoderm / cytology*,  drug effects*,  metabolism
Gene Expression / drug effects,  genetics
Homeodomain Proteins / genetics,  metabolism
Octamer Transcription Factor-3 / genetics,  metabolism
RNA, Messenger / genetics
Steroidogenic Factor 1 / genetics,  metabolism
Transcription Factors / genetics,  metabolism
Tretinoin / pharmacology*
Grant Support
Reg. No./Substance:
0/COUP Transcription Factor I; 0/COUP Transcription Factor II; 0/DAX-1 Orphan Nuclear Receptor; 0/Homeodomain Proteins; 0/Nr0b1 protein, mouse; 0/Nr2f2 protein, mouse; 0/Octamer Transcription Factor-3; 0/Pbx1 protein, mouse; 0/RNA, Messenger; 0/Steroidogenic Factor 1; 0/Transcription Factors; 0/homeobox A1 protein; 5688UTC01R/Tretinoin; 9035-51-2/Cytochrome P-450 Enzyme System; EC acid 4-hydroxylase

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