INTERACTIVE EFFECTS OF INTERLEUKIN-6, 17-BETA-ESTRADIOL AND PROGESTERONE ON GROWTH AND 17-BETA-HYDROXYSTEROID DEHYDROGENASE-ACTIVITY IN HUMAN BREAST-CARCINOMA CELLS

It has been demonstrated that reductive 17beta-hydroxysteroid dehydrogenase activity (17-HSD) in the human breast cancer cell line MCF-7 can be stimulated by 17beta-estradiol (E2), progesterone (P) and interleukin-6 (IL-6). We have examined the interactive effects of these factors on growth and reductive 17-HSD activity of MCF-7 cells cultured under defined conditions in phenol red-free medium. E2 stimulated growth of MCF-7 cells in a dose-dependent manner, while IL-6 had a growth inhibitory effect and in combination with E2, it reduced or abolished the stimulatory effects of the steroid. Both E2 and IL-6 stimulated 17-HSD activity by a maximum of 2- to 5-fold, but, in combination, the stimulatory effects ranged from 7- to 10-fold, indicating a strong synergism between the 2 factors. P had growth stimulatory effects on MCF-7, but when combined with IL-6 had no further positive or negative growth effects. Both factors stimulated reductive 17-HSD activity and simultaneous treatment with P and IL-6 indicated a synergy between the 2 factors. These results provide evidence of powerful interactive effects between steroidal and paracrine control of human breast epithelial cells in vitro.