Establishment of Novel Anti-Hormone Therapy of Breast Cancer based on the Inhibition of Uptake Transporter of Conjugated Estrogen by Cancer Cells.
| Project/Area Number |
17390046
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Medical pharmacy
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| Research Institution | TOKYO UNIVERSITY OF SCIENCE |
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Principal Investigator |
TAMAI Ikumi Tokyo University of Science, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (20155237)
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| Co-Investigator(Kenkyū-buntansha) |
MAEDA Tomoji Tokyo University of Science, Faculty of Pharmaceutical Sciences, Assistant Professor, 薬学部, 助手 (60303294)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥14,800,000 (Direct Cost: ¥14,800,000)
Fiscal Year 2006: ¥6,700,000 (Direct Cost: ¥6,700,000)
Fiscal Year 2005: ¥8,100,000 (Direct Cost: ¥8,100,000)
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| Keywords | Breast Cancer / Hormone therapy / Estrone sulfate / Transporter / Cell growth / OATP / Conjugatedestrogen / MCF7 cells / ホルモン / 生理活性 / 乳がん / エストロゲン / エストロン / MCF7 |
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| Research Abstract |
More than half of breast cancer cells exhibit estrogen-dependent growth and the estrogen receptor antagonists and aromatase inhibitors are currently used for the endocrine treatment. However, after menopausal, blood concentration of estrogens such as estradiol decreases significantly and sulfate-conjugated metabolite of estrogen, estrone-3-sulfate (E3S), becomes major estrogen precursor. So, it is possible that E3S is taken up by the cells, desulfated enzymatically, and exhibits estrone receptor activity as estrogen to facilitate the proliferation of the cells. However, E3S hardly crosses the cell membrane by passive diffusion due to hydrophilic nature and requires the transporter to be taken up by the cells. Accordingly, reducing the uptake of E3S by the breast cancer cells is expected to be effective to retard the growth of breast cancer. Uptake of radio-labeled E3S by MCF7 cells was saturable and was reduced by several anionic compounds such as BSP. In addition, E3S-dependent estrogen-receptor activity was suppressed in the presence of BSP. Furthermore, a growth of MCF7 cells was increased by E3S and the growth was reduced by the addition of BSP. These results demonstrated that E3S affects the estrogen-dependent growth of breast cancer cells and the transporter for E3S expressed in the estrogen-dependent breast cancer cells should be a novel target for the endocrine treatment of the breast cancers.
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Report
(3 results)
Research Products
(8 results)
