Suppression of cell proliferation by inhibition of estrone-3-sulfate transporter in estrogen-dependent breast cancer cells
Suppression of cell proliferation by inhibition of estrone-3-sulfate transporter in estrogen-dependent breast cancer cells
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DOI：
10.1007/s11095-005-7096-0
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发表时间：
2005-10-01
影响因子：
3.7
通讯作者：
Tamai, I
中科院分区：
文献类型：
--
作者：
Nozawa, T;Suzuki, M;Tamai, I
目的。本研究的目的是通过抑制膜转运蛋白来抑制雌激素依赖性乳腺癌的进展，膜转运蛋白介导雌激素前体3-硫酸雌酮在癌细胞中的内化。测定雌激素依赖性乳腺癌MCF-7细胞对3-硫酸雌酮的摄取，并研究不同有机阴离子对MCF-7细胞摄取3-硫酸雌酮的抑制作用。检测该抑制剂对3-硫酸雌酮诱导的报告基因转录和细胞增殖的影响。MCF-7细胞对雌酮-3-硫酸酯的摄取是饱和的，K-m值为2.32mM，摄取不依赖于Na+，并被几种阴离子化合物如溴磺酸盐所抑制。通过雌激素反应元件显着抑制雌激素反应元件报告基因的转录，抑制雌酮-3-硫酸酯诱导的细胞增殖。但是，溴磺化邻苯二甲酸二乙酯不能抑制雌酮诱导的转录激活或细胞增殖。逆转录-聚合酶链式反应分析表明，有机阴离子转运多肽(OATP)-D和OATP-E可能是运输3-硫酸雌酮的候选基因。雌酮-3-硫酸酯的摄取是由钠离子非依赖性转运体介导的(S)。雌酮-3-硫酸酯转运体抑制剂可抑制雌酮-3-硫酸酯诱导的MCF-7细胞转录和细胞增殖。这些结果为乳腺癌治疗的新策略提供了基础，通过关注负责摄取雌酮-3-硫酸酯的转运体。
Purpose. The aim of the study is to suppress the progress of estrogen-dependent breast cancer by inhibiting the membrane transporter, which mediates the internalization of estrone-3-sulfate as estrogen precursor in the cancer cells.Methods. The uptake of estrone-3-sulfate by estrogen-dependent breast cancer MCF-7 cells was measured, and inhibitory study using various organic anions on estrone-3-sulfate uptake by MCF-7 cells was conducted. The effects of the inhibitor on the transcription of reporter gene and cell proliferation induced by estrone-3-sulfate were examined.Results. The uptake of estrone-3-sulfate by MCF-7 cells was saturable with K-m value of 2.32 mu M. The uptake was Na+-independent and was inhibited by several anionic compounds such as bromosulfophthalein. Bromosulfophthalein also significantly inhibited the transcription of reporter gene via estrogen response element and cell proliferation induced by estrone-3-sulfate. However, the transcriptional activation or cell proliferation induced by estrone was not inhibited by bromosulfophthalein. Reverse transcription-polymerase chain reaction analysis revealed the expression of mRNA of organic anion transporting polypeptide (OATP)-D and OATP-E as possible candidates to transport estrone-3-sulfate.Conclusions. The uptake of estrone-3-sulfate is mediated by Na+-independent transporter(s). Inhibitor of estrone-3-sulfate transporter suppressed the transcription and cell proliferation induced by estrone-3-sulfate in MCF-7 cells. The results provide the basis of a novel strategy for breast cancer treatment by focusing on the transporter responsible for the uptake of estrone-3-sulfate.