Inhibition of stilbene estrogen-induced cell proliferation of renal epithelial cells through the modulation of insulin-like growth factor-I receptor expression.
In the present study, we have investigated the effects of stilbene estrogen, diethylstilbestrol (DES), on the proliferative activity and expression of insulin-like growth factor-I (IGF-I) receptor in Syrian hamster renal epithelial cells. DES exposure to renal epithelial cells caused both dose- and time-dependent increases in proliferative activity. We also tested the effects of antiestrogen ICI 182780 and insulin-like growth factor-I receptor (IGF-IR) antibody on cell proliferation. Cotreatment of cells with ICI 182780 (250 nM) and DES resulted in a 50% decrease in cell growth compared to DES alone. Treatment of cells with an anti-IGF-IR antibody (alpha IR3, 1 microgram/ml) also significantly reversed the growth-stimulatory effects of DES. A nuclear binding assay revealed that an enhanced level (approximately 2-fold) of [125I]IGF-I binding to nuclear protein occurred in DES treated renal epithelial cell nuclei compared to controls. IGF-I receptor gene expression analyzed by Northern blotting revealed that DES treatment increased the level of IGF-IR mRNA by 2-fold compared to controls. We also tested the effect of ICI compound on the induction of IGF-I receptor gene. The cotreatment of ICI 182780 strongly inhibited DES-induced IGF-I receptor gene expression (50-60% inhibition). Stimulation of the proliferative activity of renal epithelial cells by stilbene estrogen, its prevention by IGF-I receptor antibody, and inhibition of DES-induced proliferative activity and the expression of IGF-I receptors by ICI 182780 suggest the possibility that the stimulatory effect of DES on the proliferative activity of renal epithelial cells may be mediated through the up-regulation of IGF-I receptors.
Chen
C W
CW
Department of Environmental Health Sciences, University of Alabama at Birmingham 35294-0008, USA.
Oberley
T D
TD
Roy
D
D
D000818:Animals; D002273:Carcinogens / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D006224:Cricetinae; D004054:Diethylstilbestrol / Q000494:pharmacology*; D004847:Epithelial Cells; D015870:Gene Expression / Q000187:drug effects; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D007668:Kidney / Q000166:cytology; D007680:Kidney Neoplasms / Q000139:chemically induced; D008647:Mesocricetus; D008934:Mitogens / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D017526:Receptor, IGF Type 1 / Q000502:physiology*
D002273:Carcinogens; D008934:Mitogens; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D004054:Diethylstilbestrol; D017526:Receptor, IGF Type 1