Calcium signal as a potential clinical target for breast cancer

• Project/Area Number: 26670125
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: General pharmacology
• Research Institution: Kyushu University
• Principal Investigator: Masatsugu Oh-hora 九州大学, 生体防御医学研究所, 准教授 (40351506)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 受容体・チャネル / シグナル情報伝達系 / カルシウム

Outline of Final Research Achievements

To elucidate the function of calcium signaling in the mammary gland, we have analyzed the role of store-operated calcium entry in mammary epithelial cells using cell-type specific Stim1 or Stim2 or both knockout mice. We found that store-operated calcium entry is activated in mammary epithelial cells. We then established mice in which store-operated calcium entry is ablated in mammary epithelial cells. The mice normally grew up and no abnormality of the development of mammary gland, however, new-born pups nursed by female mice ablated both Stim1 and Stim2 in mammary epithelial cells showed severe growth retardation because of impaired secretion or production of milk. These results indicate that store-operated calcium entry is essential for the function of mammary epithelial cells.

Research Products

• [Journal Article] C-Type Lectin Receptor MCL Facilitates Mincle Expression and Signaling through Complex Formation. (2015)
  • Author(s): Miyake Y, Masatsugu OH, Yamasaki S.
  • Journal Title: J Immunol. Volume: 194 Issue: 11 Pages: 5366-74
  • DOI: 10.4049/jimmunol.1402429
  • Peer Reviewed
• [Journal Article] Impaired spatial memory and enhanced long-term potentiation in mice with forebrain-specific ablation of the Stim genes. (2015)
  • Author(s): Garcia-Alvarez G, Shetty MS, Lu B, Yap KA, Oh-hora M, Sajikumar S, Bichler Z, Fivaz M.
  • Journal Title: Front Behav Neurosci. Volume: 9
  • DOI: 10.3389/fnbeh.2015.00180
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Human Mincle Binds to Cholesterol Crystals and Triggers Innate Immune Responses. (2015)
  • Author(s): Kiyotake R, Oh-Hora M, Ishikawa E, Miyamoto T, Ishibashi T, Yamasaki S.
  • Journal Title: J Biol Chem. Volume: 290 Issue: 42 Pages: 25322-32
  • DOI: 10.1074/jbc.m115.645234
  • Peer Reviewed
• [Journal Article] Crossreactive αβ T cell receptors are the predominant targets of thymocyte negative selection. (2015)
  • Author(s): McDonald BD, Bunker JJ, Erickson SA, Oh-hora M, Bendelac A.
  • Journal Title: Immunity Volume: 43 Issue: 5 Pages: 859-869
  • DOI: 10.1016/j.immuni.2015.09.009
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Dectin-2 is a direct receptor for mannose-capped lipoarabinomannan of mycobacteria. (2014)
  • Author(s): Yonekawa A, Saijo S, Hoshino Y, Miyake Y, Ishikawa E, Suzukawa M, Inoue H, Tanaka M, Yoneyama M, Oh-Hora M, Akashi K, Yamasaki S.
  • Journal Title: Immunity Volume: 41 Issue: 3 Pages: 402-13
  • DOI: 10.1016/j.immuni.2014.08.005
  • Peer Reviewed / Open Access
• [Presentation] T-cell specific loss of store-operated calcium entry causes Th2-type chronic inflammation. (2015)
  • Author(s): Masatsugu Oh-hora, Xiuyuan Lu, Sho Yamasaki
  • Organizer: 第44回日本免疫学会学術集会
  • Place of Presentation: 札幌
  • Year and Date: 2015-11-18
• [Presentation] Role of STIM-mediated calcium signaling in immune system (2015)
  • Author(s): Masatsugu Oh-hora, Xiuyuan Lu, Sho Yamasaki
  • Organizer: The 10th International Symposium of the Institute Network
  • Place of Presentation: 札幌
  • Year and Date: 2015-07-23
  • Invited
• [Presentation] Endoplasmic reticulum calcium sensors, Stim1 and Stim2, control dendritic cell functions. (2015)
  • Author(s): Soichiro Yoshikawa, Masatsugu Oh-hora, Kensuke Miyake, Lihua Li, Takuya Ohta, Kayo Horiguchi, Yoshinori Yamanishi, Hajime Karasuyama
  • Organizer: NIPS International Workshop, TRPs and SOCs
  • Place of Presentation: 岡崎
  • Year and Date: 2015-06-04
• [Presentation] Deficiency of Stim-dependent Ca2+ entry in T cells promotes IL-4-producing follicular helper T cell differentiation and causes chronic inflammation. (2015)
  • Author(s): 大洞将嗣, 陸修遠, 山﨑晶
  • Organizer: Kyoto T cell Conference
  • Place of Presentation: 京都
  • Year and Date: 2015-05-15
• [Presentation] Endoplasmic reticulum calcium sensors, Stim1 and Stim2, control dendritic cell functions. (2014)
  • Author(s): Oh-hora M, Lu X, Mori D, Yamasaki S.
  • Organizer: 第43回日本免疫学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] Dectin-2 recognizes mycobacterial lipoarabinomannan and contributes to host defense during infection. (2014)
  • Author(s): Yonekawa A, Saijo S, Miyake Y, Ishikawa E, Suzukawa M, Yoneyama M, Oh-hora M, Yamasaki S.
  • Organizer: 第43回日本免疫学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] Molecular mechanism of Ca2+ influx by IgE/antigen stimulation in basophils. (2014)
  • Author(s): Yoshikawa S, Oh-hora M, Wakamori M, Miyake K, Li L, Horiguchi K, Ohta T, Adachi T, Yamanashi Y, Karasuyama H.
  • Organizer: 第43回日本免疫学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] Calcium signaling in chronic inflammation. (2014)
  • Author(s): Oh-hora M, Lu X, Yamasaki S.
  • Organizer: 24th Hot Spring Harbor International Symposium
  • Place of Presentation: 福岡
  • Year and Date: 2014-11-07 – 2014-11-08
• [Presentation] Mechanism of chronic inflammation by the lack of store-operated calcium entry. (2014)
  • Author(s): Oh-hora M, Lu X, Yamasaki S, Takayanagi H.
  • Organizer: FASEB Science Research Conference
  • Place of Presentation: Nassau, Bahamas
  • Year and Date: 2014-06-01 – 2014-06-06
• [Book] 医学のあゆみ (2014)
  • Author(s): 大洞将嗣
  • Total Pages: 2
  • Publisher: 医歯薬出版株式会社