Document Detail

9-cis and all-trans retinoic acid induce a similar phenotype in human teratocarcinoma cells.
MedLine Citation:
PMID:  8243889     Owner:  NLM     Status:  MEDLINE    
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-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)
J M Kurie; J Buck; T M Eppinger; D Moy; E Dmitrovsky
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Differentiation; research in biological diversity     Volume:  54     ISSN:  0301-4681     ISO Abbreviation:  Differentiation     Publication Date:  1993 Sep 
Date Detail:
Created Date:  1993-12-23     Completed Date:  1993-12-23     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0401650     Medline TA:  Differentiation     Country:  GERMANY    
Other Details:
Languages:  eng     Pagination:  123-9     Citation Subset:  IM    
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
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MeSH Terms
Cell Differentiation / drug effects,  genetics
Drug Resistance / genetics
Neurons / drug effects
Receptors, Retinoic Acid / biosynthesis
Teratocarcinoma / genetics*
Tretinoin / chemistry,  pharmacology*
Tumor Cells, Cultured
Grant Support
1F32CA08940-02/CA/NCI NIH HHS; 1RO1-CA54494-02/CA/NCI NIH HHS
Reg. No./Substance:
0/Receptors, Retinoic Acid; 302-79-4/Tretinoin

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