Investigation of biomakers for membrane-associated estrogen receptor signaling pathway in breast cancer cells using selective nano-ligand

• Project/Area Number: 15K08637
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Laboratory medicine
• Research Institution: Tohoku University
• Principal Investigator: NIWA Toshifumi 東北大学, 医学系研究科, 准教授 (90218248)
• Co-Investigator(Kenkyū-buntansha): 林 慎一 東北大学, 医学系研究科, 教授 (60144862)
• Project Period (FY): 2015-10-21 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 乳癌 / 細胞・組織 / シグナル伝達 / エストロゲン / 特異的リガンド / ホルモン療法耐性 / バイオマーカー / ナノ材料 / エストロゲン受容体 / 癌

Outline of Final Research Achievements

The function of membrane-associated estrogen receptor (mER) in breast cancer cells and relation to hormone therapy resistance were investigated using a novel selective ligand, Qdot-6-E2. It was demonstrated that Qdot-6-E2 stimulated both MAPK and PI3K-akt-mTOR phosphorylation pathways resulting cell growth. Among the estrogen depletion resistant cells with different mechanisms, only the cells maintaining nuclear ER function were sensitive to Qdot-6-E2. This suggests that mER is probably a localized form of nuclear ERα. The target genes of mER were markedly different from those of nuclear ER and we found some candidates for the specific biomarker of mER signaling pathways.

Research Products

• [Journal Article] Single CpG site methylation controls estrogen receptor gene transcription and correlates with hormone therapy resistance (2017)
  • Author(s): Tsuboi K, Nagatomo T, Gohno T, Higuchi T, Sasaki S, Fujiki N, Kurosumi M, Takei, H, Yamaguchi Y, Niwa T, Hayashi SI
  • Journal Title: J Steroid Biochem Mol Biol Volume: 171 Pages: 209-217
  • DOI: 10.1016/j.jsbmb.2017.04.001
  • Peer Reviewed
• [Presentation] ホルモン療法耐性乳癌細胞モデルにおけるエピゲノム制御によるER陰転化機構 (2017)
  • Author(s): 佐々木駿太，坪井洸樹，徳田恵美，丹羽俊文，林 慎一
  • Organizer: 第18回ホルモンと癌研究会
• [Presentation] ER 陽性乳癌細胞におけるPI3K 経路の重要性と阻害による効果検討 (2017)
  • Author(s): 小松隆幸，中村美紗都，徳田恵美，丹羽俊文，林 慎一
  • Organizer: 第25回日本乳癌学会学術総会
• [Presentation] ホルモン療法耐性乳癌細胞におけるER発現とエピゲノム制御解析 (2017)
  • Author(s): 坪井洸樹，佐々木駿太，長友隆将，郷野辰幸，樋口 徹，藤井里圭，花村 徹，山口ゆり，丹羽俊文，林 慎一
  • Organizer: 第25回日本ステロイドホルモン学会学術集会
• [Presentation] Investigation of membrane-associated estrogen receptor molecule utilizing specific ligand in breast cancer cell (2016)
  • Author(s): 鈴木奏絵，高信純子，丹羽俊文，林 慎一
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: 横浜（パシフィコ横浜）
  • Year and Date: 2016-11-30
• [Presentation] Function of membrane-associated estrogen receptorand effect on molecular targeted drugs of breast cancer (2015)
  • Author(s): 鈴木奏絵，高信純子，丹羽俊文，林 慎一
  • Organizer: 第38回日本分子生物学会年会/第88回日本生化学会大会 合同大会
  • Place of Presentation: 神戸(神戸ポートアイランド)
  • Year and Date: 2015-12-01
• [Remarks] 分子機能解析学分野
  • URL: http://www.mfd.med.tohoku.ac.jp
• [Remarks] 分子機能解析学分野
  • URL: http://www.mfd.med.tohoku.ac.jp/