Uptake transporter organic anion transporting polypeptide 1B3 contributes to the growth of estrogen-dependent breast cancer

被引:30
作者
Maeda, Tomoji [1 ,2 ,3 ]
Irokawa, Masanori [2 ]
Arakawa, Hiroshi [1 ]
Kuraoka, Erika [1 ]
Nozawa, Takashi [1 ]
Tateoka, Ryoko [4 ]
Itoh, Yoshiharu [4 ]
Nakanishi, Takeo [1 ]
Tamai, Ikumi [1 ,2 ]
机构
[1] Kanazawa Univ, Dept Membrane Transport & Biopharmaceut, Fac Pharm, Inst Med Pharmaceut & Hlth Sci, Kanazawa, Ishikawa 9201192, Japan
[2] Tokyo Univ Sci, Fac Pharmaceut Sci, Dept Mol Biopharmaceut, Chiba 2788510, Japan
[3] Iwate Med Univ, Dept Neurosci, Fac Pharmaceut Sci, Yahaba, Iwate 0203603, Japan
[4] Kureha Co, Biomed Res Labs, Shinjyuku Ku, Tokyo 1698503, Japan
关键词
Breast cancer; Estrogen; Transporter MCF-7 cells; DNA microarray; OATP; B OATP-B; HEPATIC-UPTAKE; HUMAN LIVER; AROMATASE ACTIVITIES; SULFATASE; EXPRESSION; IDENTIFICATION; PROLIFERATION; ESTRADIOL; RECEPTOR;
D O I
10.1016/j.jsbmb.2010.06.014
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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
引用
收藏
页码:180 / 185
页数:6
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