INTERLEUKIN-6 INHIBITS THE POTENT STIMULATORY ACTION OF ANDROGENS, GLUCOCORTICOIDS AND INTERLEUKIN-1-ALPHA ON APOLIPOPROTEIN-D AND GCDFP-15EXPRESSION IN HUMAN BREAST-CANCER CELLS

Our study was designed to investigate the potential interaction betwee n steroid hormones and interleukin-6 (IL-6) in the regulation of apoli poprotein D (apo-D) and gross cystic disease fluid protein 15 (GCDFP-1 5) expression in ZR-75-1 human breast cancer cells. We first observed that exposure to IL-6 for 6-14 days decreased basal apo-D and GCDFP-15 secretion by 50% and 23%, respectively. In the same experiment, such treatment with IL-6 decreased cell proliferation by approximately 40% after 6 and 14 days of incubation. Exposure to IL-6 markedly decreased dihydrotestosterone (DHT)-induced apo-D and GCDFP-15 release, with a half-maximal effect measured at 13 U/ml. A similar inhibitory action o f IL-6 was observed on the glucocorticoid dexamethasone (DEX)-induced apo-D and GCDFP-15 secretion. The sensitivity of the apo-D and GCDFP-1 5 response to the stimulatory action of DHT or DEX was, however, not c hanged by concomitant exposure to IL-6. The inhibitory effect of IL-6 on the secretion of these two biochemical markers was additive to that of 17 beta-estradiol. In addition, IL-6 blocked the stimulatory effec t of interleukin-1 alpha (IL-1 alpha) on apo-D and GCDFP-15 secretion. Our results show that IL-6 is a potent inhibitor of basal as well as androgen-, glucocorticoid- and IL-1 alpha-induced apo-D and GCDFP-15 s ecretion in ZR-75-1 human breast cancer cells, while cell proliferatio n is inhibited by this cytokine. (C) 1995 Wiley-Liss, Inc.