SYNERGISTIC INTERACTION OF GROWTH-FACTORS AND ALBUMIN IN REGULATING ESTRADIOL SYNTHESIS IN BREAST-CANCER CELLS

Estradiol 17-beta-hydroxysteroid dehydrogenase acts to convert estrone to the biologically active estrogen, estradiol, in breast tumors and MCF-7 breast cancer cells in vitro. In this study we have examined the ability of albumin to influence the effect of growth factors (insulin-like growth factor-I (IGF-I), epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha)) and cytokines (interleukin (IL)-1, IL-6) on estradiol 17-beta-hydroxysteroid dehydrogenase activity in MCF-7 cells. IGF-I (80 ng/ml) or albumin (30-mu-g/ml) stimulated estradiol 17-beta-hydroxysteroid dehydrogenase activity by 144% and 102% (p < 0.01). The combination of IGF-I and albumin, however, produced a marked (704%) synergistic stimulation of estradiol 17-beta-hydroxysteroid dehydrogenase activity. EGF or TGF-alpha failed to stimulate estradiol 17-beta-hydroxysteroid dehydrogenase activity and no synergism with albumin was detected. IL-1 (10 ng/ml), but not IL-6, also stimulated estradiol 17-beta-hydroxysteroid dehydrogenase activity and acted synergistically with albumin to stimulate enzyme activity. MCF-7 cells were shown to specifically bind I-125-albumin and binding is increased by pretreatment of cells with IGF-I (80 ng/ml) for 48 h. It is concluded that the synergism that results from treating MCF-7 cells with albumin and IGF-I may result from increased albumin uptake and subsequent biological effect.