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 micrograms/ml) stimulated estradiol 17 beta-hydroxysteroid dehydrogenase activity by 144% and 102% (p less than 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 125I-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.
Singh
A
A
Unit of Metabolic Medicine, St. Mary's Hospital Medical School, Imperial College of Science, Technology and Medicine, London, UK.
Blench
I
I
Morris
H R
HR
Savoy
L A
LA
Reed
M J
MJ
D000418:Albumins / Q000378:metabolism / Q000502:physiology*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D004815:Epidermal Growth Factor / Q000502:physiology; D004958:Estradiol / Q000096:biosynthesis*; D004960:Estradiol Dehydrogenases / Q000378:metabolism; D006133:Growth Substances / Q000502:physiology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000502:physiology; D007375:Interleukin-1 / Q000502:physiology; D015850:Interleukin-6 / Q000502:physiology; D013058:Mass Spectrometry; D016211:Transforming Growth Factor alpha / Q000502:physiology; D014407:Tumor Cells, Cultured
D000418:Albumins; D006133:Growth Substances; D007375:Interleukin-1; D015850:Interleukin-6; D016211:Transforming Growth Factor alpha; D004958:Estradiol; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I; D004960:Estradiol Dehydrogenases