High retinoid X receptor expression in JEG-3 choriocarcinoma cells: involvement in cell function modulation by retinoids.
Retinoic acid (RA) is an important mediator of cell differentiation. It stimulates hCG secretion by JEG-3 choriocarcinoma cells in vitro after a time lag. The first aim of this study was to characterize which types of retinoid receptors (RARs and RXRs) are present in JEG-3 cells. Using Western blot analysis and immunocytochemistry with specific antibodies as well as Northern blot analysis, we found that JEG-3 cells expressed RAR alpha and RXR alpha, the latter being the predominant receptor. We then analyzed the action on cell proliferation and hCG secretion of the physiological retinoids all-trans RA (RA) and 9 cis RA as well as synthetic retinoids with specific affinity for RAR alpha and RXR alpha. All these retinoids were potent inhibitors of cell growth, maximal inhibition (72 +/- 2%) being observed after 4 days of treatment with Ro 25, a RXR alpha specific ligand. Within 24 h, 9 cis RA and Ro 25 stimulated hCG secretion, and maximal stimulation (1,472 +/- 10%) occurred at 48 h with the RXR alpha-specific ligand. The RAR alpha-specific ligand also stimulated hCG secretion but to a lower extend and after a delay of 48 h. These results suggest a predominant role of RXR alpha in mediating the biological effects of retinoids on JEG-3 cells and the possible induction by RA itself of the metabolic pathway leading to 9 cis RA.
Unité INSERM 427, Faculté des Sciences Pharmaceutiques et Biologiques de Paris, Université René Descartes, France.
J
J
Guibourdenche
S
S
Roulier
C
C
Rochette-Egly
D
D
Evain-Brion
D000906:Antibodies; D015152:Blotting, Northern; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D002822:Choriocarcinoma; D006063:Chorionic Gonadotropin / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D009687:Nuclear Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D018168:Receptors, Retinoic Acid / Q000032:analysis / Q000235:genetics* / Q000276:immunology; D047488:Retinoid X Receptors; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics* / Q000276:immunology; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000737:chemistry / Q000187:drug effects / Q000502:physiology
D000906:Antibodies; D006063:Chorionic Gonadotropin; D009687:Nuclear Proteins; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors; D014212:Tretinoin