9-cis and all-trans retinoic acid induce a similar phenotype in human teratocarcinoma cells Journal Article
| Authors: | Kurie, J. M.; Buck, J.; Eppinger, T. M.; Moy, D.; Dmitrovsky, E. |
| Article Title: | 9-cis and all-trans retinoic acid induce a similar phenotype in human teratocarcinoma cells |
| Abstract: | Prior 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-β (RAR-β) and retinoid X receptor-α (RXR-α). Both retinoids prominently augmented RAR-β 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-α 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 (NTZ/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-α expression at the level of total cellular RNA. These studies establish the effectiveness of 9-cis RA as a differentiation agent of human TC cells and demonstrate that retinoids with different nuclear receptor affinities can induce similar phenotypes in NT2/D1 cells. In addition, the findings in the retinoid resistant NT2/Dl-R1 cell implicate a role for specific retinoid receptors in this human TC differentiation program. © 1993, International Society of Differentiation. All rights reserved. |
| Keywords: | controlled study; human cell; comparative study; phenotype; tumor differentiation; cell line; cell differentiation; neurons; drug resistance; tumor cells, cultured; nucleotide sequence; plasmid; cell nucleus receptor; retinoic acid; carcinoma cell; retinoid; stereoisomerism; tretinoin; receptors, retinoic acid; teratocarcinoma; repetitive dna; human; priority journal; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; retinoic acid binding protein; retinoid binding protein |
| Journal Title: | Differentiation |
| Volume: | 54 |
| Issue: | 3 |
| ISSN: | 0301-4681 |
| Publisher: | International Society of Differentiation |
| Date Published: | 1993-10-01 |
| Start Page: | 123 |
| End Page: | 129 |
| Language: | English |
| DOI: | 10.1111/j.1432-0436.1993.tb01595.x |
| PUBMED: | 8243889 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Source: Scopus |
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