Effects of retinoic acid and gamma-interferon on expression of retinoic acid receptor and cellular retinoic acid-binding protein in breast cancer cells.
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.[1]References
- Effects of retinoic acid and gamma-interferon on expression of retinoic acid receptor and cellular retinoic acid-binding protein in breast cancer cells. Widschwendter, M., Daxenbichler, G., Dapunt, O., Marth, C. Cancer Res. (1995) [Pubmed]
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