Up-regulation of nuclear IGF-I receptor by short term exposure of stilbene estrogen, diethylstilbestrol

Up-regulation of nuclear IGF-I receptor by short term exposure of stilbene estrogen, diethylstilbestrol
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DOI:
10.1016/0303-7207(96)03751-3
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发表时间:
1996-04-19
影响因子:
4.1
通讯作者:
Roy, D
Roy, D
中科院分区:
医学2区
文献类型:
--
作者:
Chen, CW;Roy, D

文献摘要

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在本研究中,我们报告了新的发现,IGF-I受体存在于细胞核的基础上的证据,从结合试验,检测受体的亲和标记和蛋白质印迹,并通过免疫荧光定位。与对照组相比,在二苯乙烯雌激素(己烯雌酚,DES)处理的仓鼠肾脏中,核IGF-I受体(nIGF-IR)的水平几乎翻了一番。对照组nIGF-IR的结合常数Kd和Bmax分别为22.1 nM和6.6 nmol/mg蛋白,而DES处理后分别改变为5.3 nM和16.3 nmol/mg蛋白(P < 0.001)。DES处理的细胞核中IGF-IR的增强水平通过亲和标记和Western印迹证实。这些数据表明IGFs可能通过存在于细胞核中的IGF-I受体发挥其生物学效应。暴露于致癌剂量的DES是否上调nIGF-IR可能是叙利亚仓鼠肾取消诱导的一个因素尚不清楚。
In the present study we report the novel findings that IGF-I receptors are present in the nucleus based on the evidence from binding assay, detection of receptors by affinity labeling and Western blotting, and localization by immunofluorescence. The level of nuclear IGF-I receptors (nIGF-IRs) almost doubled in stilbene estrogen (diethylstilbestrol, DES treated hamster kidneys compared to the controls. The binding constants K-d and B-max of nIGF-IR of controls, 22.1 nM and 6.6 nmol/mg protein, respectively, were changed in response to DES treatment to 5.3 nM and 16.3 nmol/mg protein (P < 0.001), respectively. The enhanced level of IGF-IR in DES-treated nuclei was confirmed by both affinity labeling and Western blotting. These data suggest that IGFs may exert their biological effect through the IGF-I receptor present in the nucleus. Whether the up-regulation of nIGF-IR by exposure to a carcinogenic dose of DES may be a factor in the induction of renal cancel in Syrian hamsters, is not clear.