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Effects of Retinoic Acid and -Interferon on Expression of Retinoic Acid Receptor and Cellular Retinoic Acid-binding Protein in Breast Cancer Cells¹

Department of Obstetrics and Gynecology, Innsbruck University Hospital, Anichstraße 35, A-6020 Innsbruck, Austria

Retinoids and -interferon (IFN-) have been demonstrated to synergistically amplify growth inhibition in cultured breast cancer cells. Since IFN- 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- was detected in the three breast cancer cell lines MCF-7, SKBR-3, and even in the RA-resistant BT-20 cells. RAR- and RAR- mRNA were observed in all cell lines, whereas RAR-ß 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- (10 ng/ml) increased RAR- expression but had no influence on RAR-, whereas RAR-ß was not detectable in any of the cell lines. RA (1 µM)-mediated CRABP II increase was suppressed by IFN- (10 ng/ml). These observations indicate that IFN--mediated increase in RAR- and suppression of RA-mediated CRABP II activation may play a role in synergistic inhibition of proliferation in breast cancer cell lines.

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.

² To whom requests for reprints should be addressed.

Received 12/28/94. Accepted 3/20/95.

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