PMID- 8892963 OWN - NLM STAT- MEDLINE DCOM- 19961224 LR - 20181130 IS - 0014-4827 (Print) IS - 0014-4827 (Linking) VI - 228 IP - 1 DP - 1996 Oct 10 TI - 9-cis-retinoic acid induces neuronal differentiation of retinoic acid-nonresponsive embryonal carcinoma cells. PG - 1-7 AB - 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. FAU - Yokota, Y AU - Yokota Y AD - Institute of Molecular Embryology and Genetics, Kumamoto University School of Medicine, Japan. FAU - Ohkubo, H AU - Ohkubo H LA - eng PT - Journal Article PL - United States TA - Exp Cell Res JT - Experimental cell research JID - 0373226 RN - 0 (RNA, Messenger) RN - 0 (Receptors, Retinoic Acid) RN - 0 (Retinoid X Receptors) RN - 0 (Retinoids) RN - 0 (Tetrahydronaphthalenes) RN - 0 (Transcription Factors) RN - 5688UTC01R (Tretinoin) RN - A61RXM4375 (Bexarotene) SB - IM MH - Animals MH - Bexarotene MH - Carcinoma, Embryonal/genetics/metabolism/pathology MH - Cell Differentiation/drug effects/physiology MH - Dose-Response Relationship, Drug MH - Down-Regulation MH - Mice MH - Neurons/cytology/*drug effects/metabolism MH - RNA, Messenger/genetics/metabolism MH - Receptors, Retinoic Acid/agonists/genetics/metabolism MH - Retinoid X Receptors MH - Retinoids/metabolism/pharmacology MH - Stereoisomerism MH - Tetrahydronaphthalenes/pharmacology MH - Transcription Factors/agonists/genetics/metabolism MH - Tretinoin/administration & dosage/chemistry/*pharmacology MH - Tumor Cells, Cultured EDAT- 1996/10/10 00:00 MHDA- 1996/10/10 00:01 CRDT- 1996/10/10 00:00 PHST- 1996/10/10 00:00 [pubmed] PHST- 1996/10/10 00:01 [medline] PHST- 1996/10/10 00:00 [entrez] AID - S0014-4827(96)90291-8 [pii] AID - 10.1006/excr.1996.0291 [doi] PST - ppublish SO - Exp Cell Res. 1996 Oct 10;228(1):1-7. doi: 10.1006/excr.1996.0291.