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 s ynergistically amplify growth inhibition in cultured breast cancer cel ls. Since IFN-gamma enhances effects mediated by retinoids more than v ice versa, we focused our investigations on the mRNA expression of cel lular retinoic acid-binding proteins (CRABPs) and retinoic acid recept ors (RARs), since these are the key molecules that mediate retinoid ac tion. Synergistic inhibition of cell proliferation under treatment wit h 9-cis-retinoic acid and IFN-gamma was detected in the three breast c ancer cell lines MCF-7, SKBR-3, and even in the RA-resistant BT-20 cel ls. RAR-alpha and RAR-gamma mRNA were observed in all cell lines, wher eas 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 l ines. IFN-gamma (10 ng/ml) increased RAR-gamma expression but had no i nfluence on RAR-alpha, whereas RAR-beta was not detectable in any of t he cell lines. RA (1 mu M)-mediated CRABP II increase was suppressed b y IFN-gamma (10 ng/ml). These observations indicate that IFN-gamma-med iated increase in RAR-gamma and suppression of RA-mediated CRABP II ac tivation may play a role in synergistic inhibition of proliferation in breast cancer cell lines.