Abstract |
Combination of all-trans-retinoic acid (RA) with either interferon-alpha or -gamma resulted in a synergistic amplification of the anti-proliferative effect on cultured breast cancer cells. RA could be replaced by other biologically active retinoids. The synergism was also observed for the induction of 2'-5'-oligoadenylate synthetase, an enzyme which is involved in anti-viral activity of interferons and possibly in growth regulation of tumor cells. Combination of RA with interferon-gamma increased the down-regulation of specific binding sites for [125I] interferon-gamma. On the other hand interferons had no effect on the cytoplasmic binding protein for RA. Comparing all-trans- with 9-cis-RA, the latter was more effective in inhibiting tumor cell growth and in inducing synergism with interferon-gamma. This would indicate that retinoic X receptors are more important in mediating these effects than the RA receptors (RARs). This assumption is also supported by the failure of Ro-415253, a specific RAR-alpha antagonist, to reduce the synergistic interaction of RA with interferon with respect to growth inhibition.
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Authors | C Marth, M Widschwendter, G Daxenbichler |
Journal | The Journal of steroid biochemistry and molecular biology
(J Steroid Biochem Mol Biol)
Vol. 47
Issue 1-6
Pg. 123-6
(Dec 1993)
ISSN: 0960-0760 [Print] England |
PMID | 8274426
(Publication Type: Journal Article)
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Chemical References |
- Receptors, Cytoplasmic and Nuclear
- Receptors, Retinoic Acid
- Recombinant Proteins
- Retinoid X Receptors
- Transcription Factors
- Tretinoin
- Interferon-gamma
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Topics |
- Breast Neoplasms
(drug therapy, pathology)
- Cell Division
(drug effects)
- Drug Resistance
- Drug Synergism
- Humans
- Interferon-gamma
(pharmacology)
- Receptors, Cytoplasmic and Nuclear
(physiology)
- Receptors, Retinoic Acid
(antagonists & inhibitors, physiology)
- Recombinant Proteins
- Retinoid X Receptors
- Stereoisomerism
- Transcription Factors
- Tretinoin
(metabolism, pharmacology)
- Tumor Cells, Cultured
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