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乳腺癌耐药蛋白(BCRP/ABCG2)在人类孕期及足月分娩前后胎盘组织中的表达情况。

Expression of breast cancer resistance protein (BCRP/ABCG2) in human placenta throughout gestation and at term before and after labor.

作者信息

Yeboah D, Sun M, Kingdom J, Baczyk D, Lye S J, Matthews S G, Gibb W

机构信息

Department of Obstetrics and Gynecology and Cellular and Molecular Medicine, University of Ottawa, 451 Smyth Rd, Ottawa, ON K1H 8M5, Canada.

出版信息

Can J Physiol Pharmacol. 2006 Dec;84(12):1251-8. doi: 10.1139/y06-078.

DOI:10.1139/y06-078
PMID:17487233
Abstract

Breast cancer resistance protein, BCRP, is a multidrug resistance protein that is highly expressed in the human placenta. In cancer tissues, this protein actively extrudes a wide variety of chemically and structurally unrelated chemotherapeutic drugs and other compounds. Studies in mice have shown that in the absence of BCRP activity in the placenta, there is a 2-fold increase in the uptake in BCRP substrates into fetus. This suggests that in the placenta, BCRP extrudes compounds that would otherwise cross the syncytiotrophoblast cells into fetal circulation. The purpose of this study was to examine the expression and localization of BCRP in the human placenta throughout gestation. Tissues from 6-13, 16-19, 24-29, 32-35, and 38-41 weeks of gestation were used. Real time RT-PCR analysis demonstrated that the mRNA levels of BCRP in the placenta do not change significantly as gestation progressed. However, Western blot analysis revealed that the protein levels increased towards the end of gestation. We demonstrated that BCRP is localized to the syncytiotrophoblast of the placenta and in some fetal blood vessels within the placenta. Tissues from the early stages of pregnancy (6-13 weeks) showed fewer BCRP positive blood vessels than term tissues (38-41 weeks).

摘要

乳腺癌耐药蛋白(BCRP)是一种多药耐药蛋白,在人胎盘中高度表达。在癌组织中,该蛋白可主动排出多种化学结构和化学性质均不相关的化疗药物及其他化合物。对小鼠的研究表明,若胎盘缺乏BCRP活性,胎儿对BCRP底物的摄取会增加两倍。这表明在胎盘内,BCRP可排出那些否则会穿过合体滋养层细胞进入胎儿循环的化合物。本研究的目的是检测整个孕期人胎盘中BCRP的表达及定位。研究使用了妊娠6 - 13周、16 - 19周、24 - 29周、32 - 35周和38 - 41周的组织。实时逆转录聚合酶链反应(RT-PCR)分析表明,随着孕期进展,胎盘内BCRP的mRNA水平无显著变化。然而,蛋白质印迹分析显示,蛋白水平在妊娠末期升高。我们证实BCRP定位于胎盘的合体滋养层以及胎盘内的一些胎儿血管。妊娠早期(6 - 13周)组织中BCRP阳性血管比足月组织(38 - 41周)少。

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