1. Role of COUP-TFI during retinoic acid-induced differentiation of P19 cells to endodermal cells.
- Author
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Pickens BS, Teets BW, Soprano KJ, and Soprano DR
- Subjects
- Animals, Apoptosis drug effects, Apoptosis genetics, COUP Transcription Factor I metabolism, COUP Transcription Factor II genetics, COUP Transcription Factor II metabolism, Cell Cycle drug effects, Cell Cycle genetics, Cells, Cultured, Cytochrome P-450 Enzyme System genetics, Cytochrome P-450 Enzyme System metabolism, DAX-1 Orphan Nuclear Receptor genetics, DAX-1 Orphan Nuclear Receptor metabolism, Endoderm metabolism, Gene Expression drug effects, Gene Expression genetics, Homeodomain Proteins genetics, Homeodomain Proteins metabolism, Mice, Octamer Transcription Factor-3 genetics, Octamer Transcription Factor-3 metabolism, Pre-B-Cell Leukemia Transcription Factor 1, RNA, Messenger genetics, Retinoic Acid 4-Hydroxylase, Steroidogenic Factor 1 genetics, Steroidogenic Factor 1 metabolism, Transcription Factors genetics, Transcription Factors metabolism, COUP Transcription Factor I genetics, Cell Differentiation drug effects, Cell Differentiation genetics, Endoderm cytology, Endoderm drug effects, Tretinoin pharmacology
- Abstract
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., (Copyright © 2012 Wiley Periodicals, Inc.)
- Published
- 2013
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