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Cell Growth & Differentiation, Vol 9, Issue 9 713-722, Copyright © 1998 by American Association of Cancer Research


ARTICLES

Deregulated expression of the retinoid X receptor alpha prevents muscle differentiation in P19 embryonal carcinoma cells

MA Pratt, C Crippen, K Hubbard and M Menard
Department of Pharmacology, University of Ottawa, Ontario, Canada. cpratt@uottawa.ca

We have studied the expression of the retinoid X receptor (RXR) family of receptors during the DMSO-induced differentiation of P19 murine embryonal carcinoma cells into mesoderm and muscle. RXR-alpha protein is weakly detectable in untreated P19 cells and in a mutant line of P19 cells (D3) that are resistant to DMSO-induced differentiation but begins to increase by day 3 and continues to rise gradually thereafter, whereas RXR-gamma protein is readily detected in P19 cells and decreases over the course of differentiation. Protein expression is uncoupled from mRNA levels, because DMSO induces a rapid, aggregation-independent, transient increase in RXR-alpha mRNA that diminishes by day 3 of differentiation. Thus, the expression of RXR-alpha protein is prevented at early times during DMSO-induced differentiation. Stable P19 cell clones that constitutively express RXR-alpha protein [P19(RXR-alpha)] are resistant to DMSO-induced differentiation associated with increased levels of oligonucleosomal-length DNA fragmentation. Loss of RXR-alpha expression after multiple passages results in a reversion to a DMSO-responsive phenotype. Id1 transcripts are present in P19 cells and are transiently decreased on day 2 of DMSO differentiation but remain elevated in DMSO-treated P19(RXR-alpha) and in P19 cells treated simultaneously with retinoic acid and DMSO. The mRNA for the mesoderm inducer protein Brachyury T was also deregulated in P19(RXR-alpha) cells and D3 cells compared with that of wild-type P19 cells. Together, these results show that expression of the RXR-alpha mRNA and protein in P19 cells is tightly regulated during the mesodermal/muscle differentiation of P19 cells, and that ectopic expression of the RXR-alpha protein prevents differentiation associated with increased cell death, prolonged expression of Brachyury T, and constitutive expression of Id1.





HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation
Copyright © 1998 by the American Association of Cancer Research.