THE EFFECT OF ICI-164384 AND INTERFERON-BETA ON THE GROWTH AND STEROID-RECEPTOR PROFILE OF BREAST-CANCER CELL-LINES

We investigated the effect of a concomitant treatment of ICI 164384 an d B-interferon (beta-IFN) on the growth of estrogen-receptor-positive (ER+) and estrogen-receptor negative (ER-) breast cancer cell lines an d on their steroid receptor profiles. ICI 164384 reduced cell prolifer ation not only in ER+ but also in ER- cell lines and completely suppre ssed the stimulation induced by estradiol (E(2)) in hormone-sensitive cell lines, MCF7 and T47D. When associated with beta-IFN, ICI 164384 i ncreased the inhibitory effect exerted by the low concentration of bet a-IFN. Moreover, ICI 164384, singly or in association with beta-IFN, d id not affect ER and PgR concentration in ER- cell lines, whereas in E R+ cell lines we observed an almost total disappearance of ER and PgR. In conclusion, our study seems to indicate that, although beta-IFN is able to control the proliferation of hormone-sensitive and hormone-in dependent subclones, it does not further improve the antiproliferative activity of ICI 164354. In contrast, the presence of ICI 164384, whic h does not induce the selection of resistant subclones under the same experimental conditions in which TAM does, may improve the efficacy of low concentration of beta-IFN and prevent the development of a second ary TAM-induced resistance.