雌二醇和胰岛素样生长因子-Ⅰ诱导的胰岛素样生长因子-Ⅰ受体和雌激素受体间的作用研究  

Interaction between insulin-like growth factors Ⅰ receptor and estrogen receptor induced by estradiol and insulin-like growth factors Ⅰ

作　　者：于正洪[1] 姜恩泽[2] 赵红[3] 上官俊杰[4] 王新星[1] 吕镗锋[5] 陈礼朋[6] 陈龙邦[1] 

机构地区：[1]第二军医大学南京临床医学院(南京军区南京总医院)肿瘤内科,南京210002 [2]南京大学医学院,南京210008 [3]美国西北大学医学院,芝加哥60611 [4]美国西北大学文理学院,芝加哥60611 [5]南京军区南京总医院呼吸内科,南京210002 [6]东南大学生命科学院,南京210009

出　　处：《医学研究生学报》2013年第9期907-911,共5页Journal of Medical Postgraduates

基　　金：国家自然科学基金(81272260);江苏省六大人才高峰基金(BK2009284)

摘　　要：目的研究发现,雌激素受体(estrogen receptor,ER)与配体的结合导致非核效应,雌二醇可以在所有层面上影响胰岛素样生长因子-Ⅰ(insulin-like growth factors,IGF-Ⅰ)系统。文中研究雌二醇和IGF-Ⅰ所诱导的胰岛素样生长因子-Ⅰ受体(insulin-like growth factor receptor,IGF-IR)和ER之间的相互作用。方法培养乳腺癌细胞MCF-7和NWTB3细胞,在ER和IGF-IR阳性的MCF-7细胞中转染空载体(NEO)导致IGF-IR下降,而在ER阴性的IGF-IR形成的NWTB3细胞中转染ER。免疫沉淀试验研究ER和IGF-IR相互结合,免疫印迹试验研究IGF-IR下游的信号通路激活情况,荧光显微镜下观察显示GFR-ER融合蛋白在细胞内的分布。结果 MCF-7乳腺癌细胞转染IGF-IR反义cDNA(SX13),造成细胞膜上的IGF-IR减少了50%。在NEO的细胞中,雌二醇和IGF-Ⅰ诱导了ER与IGF-IR的快速结合,而在SX13细胞中,该相互作用被遏制。在用ER转染NWTB3细胞过表达IGF-IR后,ER与IGF-IR的相互作用在15 min内被雌二醇和IGF-Ⅰ诱导。结论 ER与IGF-IR的相互作用可能对ER的非核效应至关重要。Objective Recent studies have found that estrogen receptor estrogen receptor（ER） activation by ligand binding results in events that suggest a non-genomic effect, and estrogen can affect the insulin-like growth factor- I （ IGF- I ） system. The aim of this study is to study interaction between insulin-like growth factor receptor （IGF-IR） and ER induced by estradiol and IGF- I ~ Methods Two cell lines, MCF-7 and NWTB3, were used. MCF-7 cells with ER and IGF-IR positive were transfected with empty vector （NEO） or anti-sense IGF-IR （SX13）. IGF-IR generated NWTB3 cells with negative ER were transfected with ER. Immunopre-cipitation was used to study the interaction between ER and IGF-IR. The downstream signaling activation of IGF-IR was measured by im- munoblotting. GFP-ER localization in cells was determined using live microscopy. Results IGF-IR on the cell membrane decreased 50% in MCF-7 cells after transfected with IGF-IR anti sense cDNA. In NEO cells, estradiol and IGF-I induced a rapid combination of ER and IGF- IR, and the interaction was abrogated in SX13 ceils. Following trans- fection of NWTB3 cells （overexpressing the IGF-IR） with ER, the in- teraction between ER and-IGF-IR was induced within 15 minutes by estradiol and IGF-I. Conclusion The interaction of the ER and IGF-IR may play an important role in the non-genomic effects of ER.

关 键 词：雌激素 胰岛素样生长因子 雌激素受体 

分 类 号：R737.9[医药卫生—肿瘤]