Interaction of retinoic acid and interferon-alpha in breast cancer cell lines

Retinoids and Interferons have been demonstrated to synergistically amplify the inhibition of proliferation in cultured breast cancer cells. Recently we reported that interferon-gamma (IFN-gamma) modulates the action of retinoic acid (RA): IFN-gamma increased expression of retinoic acid receptor-gamma (RAR-gamma) and suppressed the increase of retinoic acid binding protein type II (CRABP-II) expression. To improve the understanding of mechanism mediating synergism we extended our studies to the type I interferon-alpha. Synergistic inhibition of proliferation could be detected also by IFN-alpha and RA in BT-20 and SKBR-3 breast cancer cell lines but not in MCF-7 cells. Neither IFN-alpha nor any retinoid tested alone were able to increase RAR-gamma message, only the combination of both had this ability. In MCF-7 breast cancer cell lines the combination of any retinoid with IFN-alpha increased CRABP II expression level compared with the retinoids alone. In contrast with SKBR-3 and BT-20 cells a combination of ATRA with IFN-alpha markedly reduced ATRA mediated CRABP II induction. These results suggest that two factors may be responsible for synergistic action of RA and IFN-alpha: the inhibition of the CRABP II expression and an IFN-alpha/RA mediated upregulation of RAR-gamma.