Abstract
Retinoids and γ-interferon (IFN-γ) have been demonstrated to synergistically amplify growth inhibition in cultured breast cancer cells. Since IFN-γ enhances effects mediated by retinoids more than vice versa, we focused our investigations on the mRNA expression of cellular retinoic acid-binding proteins (CRABPs) and retinoic acid receptors (RARs), since these are the key molecules that mediate retinoid action. Synergistic inhibition of cell proliferation under treatment with 9-cis-retinoic acid and IFN-γ was detected in the three breast cancer cell lines MCF-7, SKBR-3, and even in the RA-resistant BT-20 cells. RAR-α and RAR-γ mRNA were observed in all cell lines, whereas RAR-β was not detectable. CRABP I message was expressed in MCF-7 cells only, but CRABP II was found in all three breast cancer cell lines. IFN-γ (10 ng/ml) increased RAR-γ expression but had no influence on RAR-α, whereas RAR-β was not detectable in any of the cell lines. RA (1 µm)-mediated CRABP II increase was suppressed by IFN-γ (10 ng/ml). These observations indicate that IFN-γ-mediated increase in RAR-γ and suppression of RA-mediated CRABP II activation may play a role in synergistic inhibition of proliferation in breast cancer cell lines.
Footnotes
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↵1 This study was supported by a grant from the University of Innsbruck and a grant from the Fonds zur Förderung der wissenschaftlichen Forschung, P8642-Med.
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↵2 To whom requests for reprints should be addressed.
- Received December 28, 1994.
- Accepted March 20, 1995.
- ©1995 American Association for Cancer Research.
Volume 55, Issue 10
