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pubmed-article:8243889pubmed:abstractTextPrior work has shown that all-trans retinoic acid (t-RA) treatment of the human teratocarcinoma (TC) cell line NTERA-2 clone D1 (abbreviated NT2/D1) induces a neuronal phenotype and other cell lineages. This study sought to explore the potential of 9-cis retinoic acid (9-cis RA) as a differentiation-inducing agent of this multipotent cell. Findings reported here show that 9-cis RA induced a phenotype similar to t-RA treatment of NT2/D1 cells. This similarity extended to their effects on the nuclear receptors retinoic acid receptor-beta (RAR-beta) and retinoid X receptor-alpha (RXR-alpha). Both retinoids prominently augmented RAR-beta expression and transactivated a reporter plasmid containing putative RAR response elements (RAREs) with direct repeats separated by five nucleotides (DR5). Both retinoids had no appreciable effect on RXR-alpha expression and both minimally transactivated a reporter plasmid containing putative RXR response elements (RXREs) with direct repeats separated by one nucleotide (DR1). These studies suggest that 9-cis RA and t-RA activate common events during retinoid-mediated NT2/D1 differentiation. This hypothesis was supported by the finding that NT2/D1 cells rendered refractory to t-RA (NT2/D1-R1) were also resistant to 9-cis RA. To discover alterations that could confer retinoid-refractoriness, retinoid receptor expression was examined in NT2/D1-R1 cells. In contrast to NT2/D1, the NT2/D1-R1 cell was found to have reduced RXR-alpha expression at the level of total cellular RNA.(ABSTRACT TRUNCATED AT 250 WORDS)lld:pubmed
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pubmed-article:8243889pubmed:authorpubmed-author:DmitrovskyEElld:pubmed
pubmed-article:8243889pubmed:authorpubmed-author:KurieJ MJMlld:pubmed
pubmed-article:8243889pubmed:authorpubmed-author:EppingerT MTMlld:pubmed
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pubmed-article:8243889pubmed:volume54lld:pubmed
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pubmed-article:8243889pubmed:pagination123-9lld:pubmed
pubmed-article:8243889pubmed:dateRevised2007-11-14lld:pubmed
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pubmed-article:8243889pubmed:year1993lld:pubmed
pubmed-article:8243889pubmed:articleTitle9-cis and all-trans retinoic acid induce a similar phenotype in human teratocarcinoma cells.lld:pubmed
pubmed-article:8243889pubmed:affiliationDepartment of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.lld:pubmed
pubmed-article:8243889pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:8243889pubmed:publicationTypeComparative Studylld:pubmed
pubmed-article:8243889pubmed:publicationTypeResearch Support, U.S. Gov't, P.H.S.lld:pubmed
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