Induction of mouse embryonal carcinoma cell differentiation and activation of the retinoic acid receptor beta 2 promoter by 1,25-dihydroxyvitamin D3.
1,25-Dihydroxyvitamin D3 (calcitriol) at 100 nmol/l elicited morphological differentiation and expression of collagen IV in mouse F9 embryonal carcinoma cells, and its effect was enhanced and accelerated by dibutyryl-cAMP (db-cAMP). The RAR beta 2 promoter was also activated, as evidenced by an increase in beta-galactosidase activity in an F9 reporter cell line with a stably integrated RAR beta 2-lacZ construct. All three effects were slower and less extensive with calcitriol than with retinoic acid, even in the presence of db-cAMP. Activation of the RAR beta 2 promoter by calcitriol required its TRE sequence, whereas db-cAMP required the CRE. TPA also activated the RAR beta 2 promoter, requiring a functional TRE. Thus, in the RAR beta 2 promoter the TRE sequence, whose function has so far been unidentified, mediates the effects of calcitriol and TPA. RAR beta 2 promoter activation by calcitriol was blocked by inhibitors of protein kinase C indicating that calcitriol elicits its effect via protein kinase C. Therefore, calcitriol induces differentiation of F9 mouse embryonal carcinoma cells at least in part by a pathway different from the classical one operative with retinoic acids.
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Institut für Physiologische Chemie I, Heinrich-Heine-Universität, Düsseldorf, Germany.
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Schulz
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D000818:Animals; D015152:Blotting, Northern; D003994:Bucladesine / Q000494:pharmacology; D002117:Calcitriol / Q000494:pharmacology*; D018236:Carcinoma, Embryonal / Q000378:metabolism / Q000473:pathology*; D002454:Cell Differentiation; D003094:Collagen / Q000235:genetics; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D051379:Mice; D011401:Promoter Regions, Genetic / Q000187:drug effects*; D011493:Protein Kinase C / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000235:genetics* / Q000378:metabolism; D019311:Staurosporine / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D017362:Cyclic AMP Response Element-Binding Protein; D018168:Receptors, Retinoic Acid; C082925:retinoic acid receptor beta; D003994:Bucladesine; D003094:Collagen; D011493:Protein Kinase C; D002117:Calcitriol; D019311:Staurosporine