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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
1992-8-10
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pubmed:databankReference |
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pubmed:abstractText |
P19 embryonal carcinoma (EC) cells differentiate when treated with retinoic acid (RA). The P19 EC-derived mutant cell line RAC65 is resistant to the differentiation-inducing activity of RA. We show that these cells express a truncated retinoic acid receptor alpha(mRAR alpha-RAC65), probably due to the integration of a transposon-like element in the RAR alpha gene. This receptor lacks 71 C-terminal amino acids and terminates in the ligand-binding domain. In CAT assays in RAC65 cells, mRAR alpha-RAC65 fails to trans-activate the RAR beta promoter, which contains a RA-response element. In wild-type P19 EC cells mRAR alpha-RAC65 functions as a dominant-negative repressor of RA-induced RAR beta activation. Gel retardation assays demonstrate that mRAR alpha-RAC65 is still able to bind to the RA-response element of the RAR beta promoter, indicating that competition with functional RARs for the same binding site leads to the observed dominant-negative effect. In addition, in two RAC65 clones in which wild-type hRAR alpha was stably transfected RA-sensitivity was restored and in one RAR beta expression could be induced by RA. Taken together, these data show that the primary cause of RA-resistance of RAC65 cells is the expression of a defective RAR alpha, which prevents the trans-activation of RA-responsive genes and results in a loss of the ability to differentiate.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0301-4681
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
49
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
27-37
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pubmed:dateRevised |
2003-11-14
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pubmed:meshHeading |
pubmed-meshheading:1320576-Animals,
pubmed-meshheading:1320576-Base Sequence,
pubmed-meshheading:1320576-Blotting, Northern,
pubmed-meshheading:1320576-Blotting, Southern,
pubmed-meshheading:1320576-Carrier Proteins,
pubmed-meshheading:1320576-Cell Differentiation,
pubmed-meshheading:1320576-Cell Line,
pubmed-meshheading:1320576-Cloning, Molecular,
pubmed-meshheading:1320576-DNA,
pubmed-meshheading:1320576-Drug Resistance,
pubmed-meshheading:1320576-Gene Expression Regulation,
pubmed-meshheading:1320576-Mice,
pubmed-meshheading:1320576-Microscopy, Fluorescence,
pubmed-meshheading:1320576-Molecular Sequence Data,
pubmed-meshheading:1320576-Neoplasm Proteins,
pubmed-meshheading:1320576-RNA, Messenger,
pubmed-meshheading:1320576-Receptors, Retinoic Acid,
pubmed-meshheading:1320576-Restriction Mapping,
pubmed-meshheading:1320576-Sequence Homology, Nucleic Acid,
pubmed-meshheading:1320576-Teratoma,
pubmed-meshheading:1320576-Transfection,
pubmed-meshheading:1320576-Tretinoin
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pubmed:year |
1992
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pubmed:articleTitle |
Retinoic acid resistance of the variant embryonal carcinoma cell line RAC65 is caused by expression of a truncated RAR alpha.
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pubmed:affiliation |
Hubrecht Laboratory, Netherlands Institute for Development Biology, Utrecht.
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pubmed:publicationType |
Journal Article
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