Department of Membrane Transport and Biopharmaceutics, Faculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Ishikawa 920-1192, Japan.
J Steroid Biochem Mol Biol. 2010 Oct;122(4):180-5. doi: 10.1016/j.jsbmb.2010.06.014. Epub 2010 Jul 6.
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 estrone-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 estrone-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.
硫酸雌酮-3 是绝经后妇女体内最丰富的雌激素前体之一。我们之前曾表明，硫酸雌酮-3 转运体存在于人乳腺癌衍生的 MCF-7 细胞中（《药理学与实验治疗学杂志》311（2004）1032-1037），并且抑制硫酸雌酮-3 的摄取会导致细胞生长受到抑制（《药物研究》22（2005）1634-1641）；因此，硫酸雌酮-3 转运体应该成为治疗激素依赖性乳腺癌的新靶点。本研究的目的是鉴定负责乳腺癌细胞摄取硫酸雌酮-3 的转运体。我们获得了 MCF-7 细胞的两个亚克隆，它们具有不同的硫酸雌酮-3 摄取活性，并通过 DNA 微阵列分析寻找差异表达的转运体基因。在鉴定的几个候选转运体中，进一步评估了 OATP1B3，因为 MCF-7 细胞中硫酸雌酮-3 的摄取特征似乎与 OATP1B3 的转运特性一致。通过相对活性因子（RAF）法检查 MCF-7 细胞中 OATP1B3 对硫酸雌酮-3 摄取的贡献，并计算出其贡献量为 6%。这一结果表明，OATP1B3 是为雌激素依赖性乳腺癌细胞提供雌激素前体硫酸雌酮-3 的转运体之一。
