NDLI: Blocking activator protein-1 activity, but not activating retinoic acid response element, is required for the antitumor promotion effect of retinoic acid.

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Blocking activator protein-1 activity, but not activating retinoic acid response element, is required for the antitumor promotion effect of retinoic acid.

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Blocking activator protein-1 activity, but not activating retinoic acid response element, is required for the antitumor promotion effect of retinoic acid.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Flavell, R. A. Ma, W. Y. Dong, Z. Huang, C. Rincon, M. Dawson, M. I.
Description	Author Affiliation: Huang C ( The Hormel Institute, University of Minnesota, 801 16th Avenue, N.E., Austin, MN 55912, USA.);
Abstract	Retinoic acid is one of the most promising drugs for chemotherapy and chemoprevention of cancer. Either blocking activator protein-1 (AP-1) activity or activating retinoic acid response element (RARE) have been proposed to be responsible for its antitumor activity. However, evidence for this hypothesis is lacking in vivo studies. To address this issue, we used an AP-1-luciferase transgenic mouse as a carcinogenesis model and new synthetic retinoids that are either selective inhibitors of AP-1 activation or selective activators of the RARE. The results showed that the SR11302, an AP-1 inhibition-specific retinoid, and other AP-1 inhibitors such as trans-retinoic acid and fluocinolone acetonide, markedly inhibit both 12-O-tetradecanoylphorbol-13-acetate-induced papilloma formation and AP-1 activation in 7,12-dimethyl benz(a)anthracene-initiated mouse skin (P < 0.05). In contrast, repeated applications of SR11235, a retinoid with RARE transactivating activity, but devoid of AP-1 inhibiting effect, did not cause significant inhibition of papilloma formation and AP-1 activation (P > 0.05). These results provide the first in vivo evidence that the antitumor effect of retinoids is mediated by blocking AP-1 activity, but not by activation of RARE.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	11
Volume Number	94
Language	English
Publisher	National Academy of Sciences
Publisher Date	1997-06-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Anticarcinogenic Agents Pharmacology Papilloma Prevention & Control Retinoids Skin Neoplasms Transcription Factor AP-1 Antagonists & Inhibitors Transcriptional Activation Drug Effects Tretinoin 9,10-Dimethyl-1,2-benzanthracene Animals Carcinogens Fluocinolone Acetonide Analogs & Derivatives Luciferases Biosynthesis Mice Mice, Transgenic Chemically Induced Recombinant Fusion Proteins Regulatory Sequences, Nucleic Acid Tetradecanoylphorbol Acetate Genetics Research Support, Non-U.S. Gov't Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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