PAAn-1b and PAAn-E: Two Phosphorothioate Antisense Oligodeoxynucleotides Inhibit Human Aromatase Gene Expression
Identifieur interne : 004050 ( Main/Exploration ); précédent : 004049; suivant : 004051PAAn-1b and PAAn-E: Two Phosphorothioate Antisense Oligodeoxynucleotides Inhibit Human Aromatase Gene Expression
Auteurs : P. Auvray [France] ; P. Sourdaine [France] ; G. E. Séralini [France]Source :
- Biochemical and Biophysical Research Communications [ 0006-291X ] ; 1998.
Abstract
Estrogen-dependent diseases, especially breast cancers, are frequently treated with aromatase inhibitors. Another more recent strategy is the antisense technology. In this study, after predicting aromatase mRNA secondary structure, we describe the design, the efficiency, and the toxicity of two antisense phosphorothioate oligodeoxynucleotides (PAAn-1b and PAAn-E) directed toward aromatase mRNA. Indeed, 2 μM PAAn-1b and PAAn-E encapsulated with 54 μM polyethylenimine inhibit aromatase activity by 71 and 79%, respectively, in transfected 293 cells, with IC50values of 0.2 and 0.6 μM. The mechanism of inhibition appears to be specific after using sense and scramble oligodeoxynucleotides as controls and largely decreases aromatase mRNA and protein amounts. Moreover, PAAn-1b and PAAn-E are not cytotoxic for 293 cells. This study finally provides a new strategy for aromatase inhibition. It offers new tools for studying aromatase gene expression and its role in cancer for instance, and this could be of help for the therapy of estrogen-dependent diseases.
Url:
DOI: 10.1006/bbrc.1998.9683
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Another more recent strategy is the antisense technology. In this study, after predicting aromatase mRNA secondary structure, we describe the design, the efficiency, and the toxicity of two antisense phosphorothioate oligodeoxynucleotides (PAAn-1b and PAAn-E) directed toward aromatase mRNA. Indeed, 2 μM PAAn-1b and PAAn-E encapsulated with 54 μM polyethylenimine inhibit aromatase activity by 71 and 79%, respectively, in transfected 293 cells, with IC50values of 0.2 and 0.6 μM. The mechanism of inhibition appears to be specific after using sense and scramble oligodeoxynucleotides as controls and largely decreases aromatase mRNA and protein amounts. Moreover, PAAn-1b and PAAn-E are not cytotoxic for 293 cells. This study finally provides a new strategy for aromatase inhibition. It offers new tools for studying aromatase gene expression and its role in cancer for instance, and this could be of help for the therapy of estrogen-dependent diseases.</div></front></TEI><affiliations><list><country><li>France</li></country></list><tree><country name="France"><noRegion><name sortKey="Auvray, P" sort="Auvray, P" uniqKey="Auvray P" first="P." last="Auvray">P. Auvray</name></noRegion><name sortKey="Seralini, G E" sort="Seralini, G E" uniqKey="Seralini G" first="G. E." last="Séralini">G. E. Séralini</name><name sortKey="Sourdaine, P" sort="Sourdaine, P" uniqKey="Sourdaine P" first="P." last="Sourdaine">P. Sourdaine</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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