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  • Title: Effects of retinoic acid and gamma-interferon on expression of retinoic acid receptor and cellular retinoic acid-binding protein in breast cancer cells.
    Author: Widschwendter M, Daxenbichler G, Dapunt O, Marth C.
    Journal: Cancer Res; 1995 May 15; 55(10):2135-9. PubMed ID: 7743514.
    Abstract:
    Retinoids and gamma-interferon (IFN-gamma) have been demonstrated to synergistically amplify growth inhibition in cultured breast cancer cells. Since IFN-gamma 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-gamma was detected in the three breast cancer cell lines MCF-7, SKBR-3, and even in the RA-resistant BT-20 cells. RAR-alpha and RAR-gamma mRNA were observed in all cell lines, whereas RAR-beta 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-gamma (10 ng/ml) increased RAR-gamma expression but had no influence on RAR-alpha, whereas RAR-beta was not detectable in any of the cell lines. RA (1 microM)-mediated CRABP II increase was suppressed by IFN-gamma (10 ng/ml). These observations indicate that IFN-gamma-mediated increase in RAR-gamma and suppression of RA-mediated CRABP II activation may play a role in synergistic inhibition of proliferation in breast cancer cell lines.
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