Impact of transporters for uptake of estrogen precursors on progression of breast cancer cells

• Project/Area Number: 25893224
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Biological pharmacy
• Research Institution: International University of Health and Welfare
• Principal Investigator: JUN Matsumoto 国際医療福祉大学, 薬学部, 助手 (60709012)
• Co-Investigator(Renkei-kenkyūsha): ISHII Itsuko 千葉大学医学部附属病院, 薬剤部, 教授 (00202929) ; ARIYOSHI Noritaka 千葉大学医学部附属病院, 薬剤部, 准教授 (00243957)
• Research Collaborator: TAMAI Ikumi 金沢大学, 薬学系, 教授 (20155237) ; NAKANISHI Takeo 金沢大学, 薬学系, 准教授 (30541742) ; NAGASHIMA Takeshi 千葉大学医学部附属病院, 臓器制御外科学, 准教授 (60292710) ; SAKAKIBARA Masahiro 千葉大学医学部附属病院, 臓器制御外科学, 助教 (70375632)
• Project Period (FY): 2013-08-30 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 有機アニオン輸送ポリペプチド / エストロゲン前駆体 / 乳がん / エストロゲン受容体 / 分子生物学的研究 / トランスポーター

Outline of Final Research Achievements

In this study, we investigated the relationship between expression of transporters for estrogen precursors and cell proliferation in estrogen receptor (ER)-positive breast cancer to establish a novel target and biomarker for ER-positive breast cancer. Organic anion transporting polypeptide (OATP) 2B1 has been reported to recognize various types of organic anions as substrates and has unique substrate specificity with high affinity to several estrogen precursors, including estrone sulfate (E1S). We found that the expression level of OATP2B1 was related to progression of ER-positive breast cancers and OATP2B1 has a key role in uptake of E1S in ER-positive breast cancer cells. The findings in this study lead us to conclude that OATP2B1 is involved in cell proliferation of ER-positive breast cancer by increasing the amount of estrogens derived from E1S in breast cancer cells. Moreover, OATP2B1 may be useful as a novel target or biomarker for ER-positive breast cancer.

Research Products

• [Journal Article] Organic anion transporting polypeptide 2B1 expression correlates with uptake of estrone-3-sulfate and cell proliferation in estrogen receptor-positive breast cancer cells (2015)
  • Author(s): Jun Matsumoto, Noritaka Ariyoshi, Masahiro Sakakibara, Takeo Nakanishi, Yoshiyuki Okubo, Nobumitsu Shiina, Kaoru Fujisaki, Takeshi Nagashima, Yukio Nakatani, Ikumi Tamai, Harumi Yamada, Hiroshi Takeda and Itsuko Ishii
  • Journal Title: Drug Metabolism and Pharmacokinetics Volume: 30 Issue: 2 Pages: 133-141
  • DOI: 10.1016/j.dmpk.2014.10.005
  • NAID: 210000170465
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Uptake of an Estrogen Precursor in Estrogen Receptor-Positive Breast Cancer Cells: Focusing on Organic Anion Transporting Polypeptide 2B1 (2015)
  • Author(s): Jun Matsumoto, Noritaka Ariyoshi, Masahiro Sakakibara, Takeo Nakanishi, Yoshiyuki Okubo, Nobumitsu Shiina, Kaoru Fujisaki, Yukio Nakatani, Ikumi Tamai, Takeshi Nagashima, Harumi Yamada, Hiroshi Takeda and Itsuko Ishii
  • Organizer: World congress on Pharmacology
  • Place of Presentation: Brisbane, Australia
  • Year and Date: 2015-07-20 – 2015-07-22
• [Presentation] 新規創薬ターゲットおよびバイオマーカーの確立を目指した乳がんにおけるestrogen前駆体取り込み機構の解明 (2014)
  • Author(s): 松本准、有吉範高、榊原雅裕、中西猛夫、石井伊都子、山田治美、武田弘志
  • Organizer: 第4回国際医療福祉大学学会学術大会
  • Place of Presentation: 日本、栃木
  • Year and Date: 2014-08-30 – 2014-08-31
• [Presentation] Impact of OATP2B1 expression on cell proliferation in ER-positive breast cancer.
  • Author(s): Jun Matsumoto, Noritaka Ariyoshi, Masahiro Sakakibara, Takeo Nakanishi, Ikumi Tamai, Takeshi Nagashima and Itsuko Ishii.
  • Organizer: 10th International ISSX Meeting
  • Place of Presentation: Toronto, Canada