MODULATION OF MARKERS ASSOCIATED WITH TUMOR AGGRESSIVENESS IN HUMAN BREAST-CANCER CELL-LINES BY N-(4-HYDROXYPLENYL)RETINAMIDE

The retinoid N-(hydroxyphenyl)retinamide (4-HPR) appears to be a promi sing tool for chemoprevention of breast carcinoma, and clinical trials to evaluate its effect are in progress. However, its action on tumor cells has remained largely undefined. We report here that 4-HPR induce d apoptosis and/or differentiation in breast cancer cell lines, indepe ndent of hormone receptor status and retinoic acid receptor expression , although it was slightly more efficient in inhibiting proliferation of estrogen receptor-positive cells. 4-HPR up-modulated expression of several differentiation markers (class I HLA, laminin, and beta(1) int egrin chain) and down-regulated expression of molecules associated wit h tumor progression, including the p185/HER2 oncoprotein, the epiderma l growth factor receptor, and the M(r) 67,000 laminin receptor. These data suggest that 4-HPR could exert a beneficial effect by inhibiting well proliferation and modulating breast tumor agressiveness.