9-cis-retinoic acid induces neuronal differentiation of retinoic acid-nonresponsive embryonal carcinoma cells.
P19 mouse embryonal carcinoma cells differentiate into neurons and glial cells when treated with retinoic acid. In contrast, a subline of the P19 cells, RAC65, is known to show little sign of differentiation with the treatment. We treated the two embryonal carcinoma (EC) cell lines with 9-cis-retinoic acid and investigated its neuron-inducing activity. In P19 cells, 9-cis-retinoic acid showed an activity equal to that of all-trans-retinoic acid. However in RAC65 cells, 9-cis-retinoic acid induced neurons 10-fold more effectively than all-trans-retinoic acid. The order in which various retinoids appeared in P19 cells corresponded to that of retinoic acid receptors, and the order in RAC65 cells to that of retinoid X receptors (RXRs). Furthermore we found that the down-regulation of retinoid X receptor-gamma mRNA expression was associated with neuronal differentiation in both embryonal carcinoma cell lines. In addition, a synthetic RXR-selective retinoid induced neurons from both EC cells. Our findings support an intriguing possibility that the 9-cis-retinoic acid/retinoid X receptor system may play an important role in neural differentiation.
Institute of Molecular Embryology and Genetics, Kumamoto University School of Medicine, Japan.
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Yokota
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Ohkubo
D000818:Animals; D000077610:Bexarotene; D018236:Carcinoma, Embryonal / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D047488:Retinoid X Receptors; D012176:Retinoids / Q000378:metabolism / Q000494:pharmacology; D013237:Stereoisomerism; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D014157:Transcription Factors / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D014212:Tretinoin / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D012176:Retinoids; D013764:Tetrahydronaphthalenes; D014157:Transcription Factors; D014212:Tretinoin; D000077610:Bexarotene