Uptake transporter organic anion transporting polypeptide 1B3 contributes to the growth of estrogen-dependent breast cancer
Uptake transporter organic anion transporting polypeptide 1B3 contributes to the growth of estrogen-dependent breast cancer
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DOI：
10.1016/j.jsbmb.2010.06.014
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发表时间：
2010-10-01
影响因子：
4.1
通讯作者：
Tamai, Ikumi
中科院分区：
文献类型：
--
作者：
Maeda, Tomoji;Irokawa, Masanori;Tamai, Ikumi
硫酸雌酮是绝经后妇女体内最丰富的雌激素前体之一。我们之前的研究表明，雌激素-3-硫酸盐转运体存在于人乳腺癌来源的MCF-7细胞中(J Pharmacol。Exp. Ther. 311(2004) 1032-1037)，抑制雌酮-3-硫酸摄取导致细胞生长受到抑制（Pharm Res 22 (2005) 1634-1641）；因此，雌激素-3-硫酸酯转运体可能成为激素依赖性乳腺癌治疗的新靶点。本研究的目的是鉴定乳腺癌细胞中负责摄取雌酮-3-硫酸酯的转运蛋白，我们获得了两个具有不同雌酮-3-硫酸酯摄取活性的MCF-7细胞亚克隆，并通过DNA微阵列分析寻找差异表达的转运蛋白基因。由于MCF-7细胞对雌酮-3-硫酸酯的摄取特性与OATP1B3的转运特性一致，通过相对活性因子（RAF）法检测OATP1B3对MCF-7细胞摄取雌酮-3-硫酸酯的贡献，计算得出OATP1B3对MCF-7细胞摄取雌酮-3-硫酸酯的贡献为6%。这一结果表明OATP1B3是雌激素前体雌酮-3-硫酸酯向雌激素依赖性乳腺癌细胞供应的转运蛋白之一(C) 2010 Elsevier Ltd All rights reserved
Estrone-3-sulfate is one of the most abundant estrogen precursors in postmenopausal women. We previously showed that estrone-3-sulfate transporters are present in human breast cancer-derived MCF-7 cells (J Pharmacol. Exp. Ther. 311 (2004) 1032-1037) and that inhibition of estrone-3-sulfate uptake resulted in the suppression of cell growth (Pharm Res 22 (2005) 1634-1641); therefore, estrone-3-sulfate transporter should be a novel target for therapy of hormone-dependent breast cancers. The purpose of the present study is to identify the transporter(s) responsible for the uptake of estrone-3-sulfate in breast cancer cells We obtained two subclones of MCF-7 cells with different estronc-3-sulfate uptake activities and searched for differentially expressed transporter genes by means of DNA microarray analysis Among several candidate transporters identified, OATP1B3 was further evaluated, since the uptake characteristics of estronc-3-sulfate by MCF-7 cells seemed consistent with the transport properties of OATP1B3 The contribution of OATP1B3 to estrone-3-sulfate uptake by MCF-7 cells was examined by the relative activity factor (RAF) method, and was calculated to amount to 6%. This result suggests that OATP1B3 is one of the transporters contributing to the supply of the estrogen precursor estrone-3-sulfate to estrogen-dependent breast cancer cells (C) 2010 Elsevier Ltd All rights reserved