Identificationof novel diagnostic and therapeutic factors for endocrine therapy-resistant breast cancer by next-generation sequencing strategy

• Project/Area Number: 24701033
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Clinical oncology
• Research Institution: Kagoshima University
• Principal Investigator: IJICHI Nobuhiro 鹿児島大学, 大学院・医歯学総合研究科, 助教 (80380624)
• Project Period (FY): 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2012: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 内分泌療法 / 乳がん / エストロゲン / FOXP1 / 次世代シーケンサー / FOXA1 / Erα / タモキシフェン耐性

Research Abstract

To identify the novel diagnostic and therapeutic factors for endocrine therapy-resistant breast cancer, we focused on FOXP1, one of a forkhead transcription factor family, as a candidate, and its genome-wide distributionin ERα-positive breast cancer MCF-7 cells was examined by next-generation sequencing strategy. We demonstrated that majority of binding regions of FOXP1 in MCF-7 cells stimulated with estrogen were overlapped with those of both Erαand FOXA1. We also demonstrated that the double-positive immunoreactivities of FOXP1 and FOXA1 are significantly associated with a favorable prognosis for survival of breast cancer patients receiving adjuvant tamoxifen therapy. In this study, we revealed that, similar to FOXA1, FOXP1 is assumed to be a critical transcription factor for Erαsignaling, and both forkhead transcription factors can serve as predictive factors for acquired endocrine resistance in breast cancer.

Research Products

• [Journal Article] Association of double-positive FOXA1 and FOXP1 immunoreactivities with favorable prognosis of tamoxifen-treated breast cancer patients (2012)
  • Author(s): Ijichi N, Shigekawa T, Ikeda K,Horie-Inoue K, Shimizu C, Saji S, Aogi K, Tsuda H, Osaki A, Saeki T, Inoue S
  • Journal Title: Horm Cancer Volume: 3 Issue: 4 Pages: 147-159
  • DOI: 10.1007/s12672-012-0111-0
  • Peer Reviewed
• [Journal Article] Forkhead box transcription factor, forkhead box A1, shows negative association with lymph node status in endometrial cancer, and represses cell proliferation and migration of endometrial cancer cells (2012)
  • Author(s): Abe Y, Ijichi N, Ikeda K, Kayano H, Horie-Inoue K, Takeda S, Inoue S
  • Journal Title: Cancer Sci Volume: 103 Issue: 4 Pages: 806-812
  • DOI: 10.1111/j.1349-7006.2012.02201.x
  • Peer Reviewed
• [Presentation] フォークヘッド転写因子FOXP1 の全ゲノムにおける結合部位同定による ER シグナル調節機構の解析 (2012)
  • Author(s): 伊地知暢広、堀江公仁子、池田和博、大石貴史、井上聡
  • Organizer: 第20回日本ステロイドホルモン学会
  • Place of Presentation: 石川
  • Year and Date: 2012-11-18
• [Presentation] EBAG9 immunoreactivity is a potential prognostic factor for poor outcome of breast cancer patients with adjuvant tamoxifen therapy (2012)
  • Author(s): Shigekawa T, Ijichi N, Ikeda K, Miyazaki T, Horie-Inoue K, Shimizu C, Saji S, Aogi K, Tsuda H, Osaki A, Saeki T, Inoue S
  • Organizer: 35th San Antonio Breast Cancer Symposium, San Antonio
  • Place of Presentation: Texas, USA
• [Presentation] ホルモン療法抵抗性前立腺がん細胞におけるエネルギー代謝関連核内受容体作用の検討 (2012)
  • Author(s): 堀江公仁子、高山賢一、伊地知暢広、池田和博、井上聡
  • Organizer: 脳心血管抗加齢研究会2012
  • Place of Presentation: 大阪
• [Presentation] フォークヘッド転写因子FOXP1の全ゲノムにおける結合部位同定によるERシグナル調節機構の解析 (2012)
  • Author(s): 伊地知 暢広
  • Organizer: 第20回日本ステロイドホルモン学会学術集会
  • Place of Presentation: 石川県金沢市
• [Book] HORMONES AND BREAST CANCER, Elsevier
  • Author(s): Ijichi N, Ikeda K, Horie-Inoue K, Inoue S
  • Publisher: (in press)