An ovarian carcinoma model using immortalized human ovarian surface epithelial cells without chromosomal instability

• Project/Area Number: 18390450
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Kumamoto University
• Principal Investigator: KATABUCHI Hidetaka Kumamoto University, 大学院・医学薬学研究部, 教授 (90224451)
• Co-Investigator(Kenkyū-buntansha): HIRONORI Tashiro 熊本大学, 医学部・附属病院, 講師 (70304996) ; HIDEYUKI Ohtake 熊本大学, 医学部・附属病院, 助教 (60336237)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥13,260,000 (Direct Cost: ¥11,400,000、Indirect Cost: ¥1,860,000); Fiscal Year 2008: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000); Fiscal Year 2007: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2006: ¥5,200,000 (Direct Cost: ¥5,200,000)
• Keywords: 細胞・組織 / 遺伝子 / 癌 / 上皮性卵巣癌 / 不死化 / 類内膜腺癌 / 明細胞腺癌 / PI3 / Pten / Wnt / β-catenin / k-ras / 不死化ヒト卵巣表層上皮細胞株 / HPV E7 / hTERT導入 / 上皮生卵巣癌 / PI3K / Wint / K-ras

Research Abstract

上皮性卵巣癌(卵巣癌)の多くは、卵巣表層上皮(OSE)細胞から発生すると考えられているが、このOSEから発癌に至る過程は今なお明らかではない。われわれは、世界で初めてウイルス癌遺伝子を用いない染色体安定性の新規不死化ヒトOSE細胞株(HOSEC)を樹立した。卵巣癌で多く報告されている遺伝子異常をこのHOSECに導入し、免疫不全マウスの腹腔内に移植することで、ヒト卵巣癌を模倣した播種病巣を形成させることができる卵巣癌実験モデルを構築した。この実験モデルは、卵巣癌の発癌機構の解明とともに発癌に関わる分子をターゲットとした新規治療薬の開発を可能とする。

Research Products

• [Journal Article] Oncogenic transformation of human ovarian surface epithelial cells with defined cellular oncogenes (2009)
  • Author(s): Sasaki R, Narisawa-Saito M, Yugawa T, Fujita M, Tashiro H, Katabuchi H, Kiyono T
  • Journal Title: Carcinogenesis 30 Pages: 423-431
  • Peer Reviewed
• [Journal Article] Detection of M2 macrophages and colony- stimulating factor 1 expression in serous and mucinous ovarian epithelial tumors (2009)
  • Author(s): Kawamura K, Komohara Y, Takaishi K, Katabuchi H, Takeya M
  • Journal Title: Pathol Int (in press)
  • NAID: 10027380027
  • Peer Reviewed
• [Journal Article] Oncogenic transformation of human ovarian surface epithelial cells with defined cellular oncogenes. (2009)
  • Author(s): Sasaki R
  • Journal Title: Carcinogenesis 30 Pages: 423-431
  • Peer Reviewed
• [Journal Article] Neurofibromin 1(NF1)defects are common in human ovarian serous carcinomas and co-occur with TP53 mutations (2008)
  • Author(s): Sangha N, Wu R, Kuick R, Powers S, Mu D, Fiander D, Yuen K, Katabuchi H, Tashiro H, Fearon ER, Cho KR
  • Journal Title: Neoplasia 10 Pages: 1362-1372
  • Peer Reviewed
• [Journal Article] Germ cell specific protein VASA is over-expressed in epithelial ovarian cancer and disrupts DNA damage-induced G2 checkpoint (2008)
  • Author(s): Hashimoto H, Sudo T, Mikami Y, Otani M, Takano M, Tsuda H, Itamochi H, Katabuchi H, Ito M, Nishimura R
  • Journal Title: Gynecol Oncol 111 Pages: 312-319
• [Journal Article] Mouse model of human ovarian endometrioid adenocarcinoma based on somatic defects in the Wnt/beta-catenin and PI3K/Pten signaling pathways (2007)
  • Author(s): Wu R, Hendrix-Lucas N, Kuick R, Zhai Y, Schwartz DR, Akyol A, Hanash S, Misek DE, Katabuchi H, Williams BO, Fearon ER, Cho KR
  • Journal Title: Cancer Cell 11 Pages: 321-333
  • Peer Reviewed
• [Journal Article] Mouse model of human ovarian endometrioid adenocarcinoma based on somatic defe-cts in the Wnt/beta-Catenin and PI3K/Pten signaling pathways. (2007)
  • Author(s): R. Wu
  • Journal Title: Cancer Cell 11 Pages: 321-333
  • Peer Reviewed
• [Journal Article] 顕微鏡からみえてくる卵巣癌研究の対象と新戦略 (2007)
  • Author(s): 片渕 秀隆
  • Journal Title: 日本産科婦人科学会熊本地方部会雑誌 51 Pages: 13-28
  • Peer Reviewed
• [Journal Article] Mouse model of human ovarian endometrioid adenocarcinoma based on somatic defects in the Wnt/beta-Catenin and PI3K/Pten singaling pathways. (2007)
  • Author(s): R.Wu, N.Hendrix-Lucas, R.Kuick, Y.Zhai, DR.Schwartz, A.Akyol, S.Hanash, DE.Misek, H.Katabuchi
  • Journal Title: Cancer Cell 11 Pages: 321-333
• [Journal Article] Classifications of ovarian cancer tissues by proteomic patterns (2006)
  • Author(s): Zhu Y, Wu R, Sangha N, Yoo C, Cho KR, Shedden KA, Katabuchi H, Lubman DM
  • Journal Title: Proteomics 6 Pages: 5846-5856
  • Peer Reviewed
• [Journal Article] Structural changes and cell properties of human ovarian surface epithelium in ovarian pathophysiology (2006)
  • Author(s): Okamura H, Katabuchi H, Nitta M, Ohtake H
  • Journal Title: Microsc Res Tech 69 Pages: 469-481
  • Peer Reviewed
• [Journal Article] Homozygous deletion of MKK4 in ovarian serous carcinoma (2006)
  • Author(s): Nakayama K, Nakayama N, Davidson B, Katabuchi H, Kurman RJ, Velculescu VE, Shih IeM, Wang TL
  • Journal Title: Cancer Biol Ther 5 Pages: 630-634
  • Peer Reviewed
• [Journal Article] Homozygous deletion of MKK4 in ovarian serous carcinoma (2006)
  • Author(s): K.Nakayama, N.Nakayama, B.Davidson, H.Katabuchi
  • Journal Title: Cancer Biology and Therapy 5 Pages: 630-634
• [Journal Article] Structural changes and properties of human ovarian surface epithelium in ovarian pathophysiology (2006)
  • Author(s): H.Okamura, H.Katabuchi, M.Nitta, H.Ohtake
  • Journal Title: Microscopy Research and Technique 69 Pages: 469-481
• [Presentation] Current Status of Gynecologic Cancer in Asia (2008)
  • Author(s): Katabuchi H
  • Organizer: 7^<th> Korea-Japan Gynecologic Cancer Joint Meeting
  • Place of Presentation: Korea
  • Year and Date: 2008-11-27
• [Presentation] Establishment of a model for epithelial ovarian cancer using normal human ovarian surface epithelial cells (2008)
  • Author(s): Sasaki R
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: パシフイコ横浜
  • Year and Date: 2008-10-28
• [Presentation] 不死化ヒト卵巣表層上皮細胞株(HOSE)を用いた上皮性卵巣癌の組織発生の解析(高得点演題採択) (2008)
  • Author(s): 佐々木瑠美
  • Organizer: 第60回 日本産科婦人科学会学術講演会
  • Place of Presentation: パシフイコ横浜
  • Year and Date: 2008-04-13
• [Presentation] Human ovarian surface epithelial cell lines: A new tool to understand the pathogenesis of epithelial ovarian cancer (2008)
  • Author(s): Katabuchi H
  • Organizer: 10^<th> Symposium Japanese- German Society of Obstetrics and Gynecology
  • Place of Presentation: Germany
• [Presentation] ヒト正常卵巣表層上皮細胞を用いた上皮性卵巣癌の発癌機構の解析 (2008)
  • Author(s): 佐々木瑠美, 他
  • Organizer: 第60回日本産科婦人科学会
  • Place of Presentation: 横浜
• [Presentation] Cytoreductionのための骨盤腹膜切除術pelvic peritonectomy : 子宮を軸としたマンシェット型切除術 (2008)
  • Author(s): 片渕秀隆
  • Organizer: 第30回日本産婦人科手術学会
  • Place of Presentation: 京都
• [Presentation] 顕微鏡からみえてくる卵巣癌 (2007)
  • Author(s): 片渕秀隆
  • Organizer: 研究の対象と新戦略NHO-GSG婦人科腫瘍セミナー
  • Place of Presentation: 京都
  • Year and Date: 2007-10-25
• [Presentation] Development of in vitro models for epithelial ovarian carcinoma with immortaliz-ed human ovarian surface epithelial cells. (2007)
  • Author(s): R. Sasaki
  • Organizer: 66^<th> annual meeting of the Japanese Cancer Association
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-05
• [Presentation] 腹腔マクロファージによる上皮性卵巣癌の発癌・進展機構への関与 (2007)
  • Author(s): 河村 京子
  • Organizer: 日本産科婦人科学会
  • Place of Presentation: 東京
  • Year and Date: 2007-04-16
• [Presentation] Human ovarian surface epithelial cell lines: A new tool to understand the pathogenesis of epithelial ovarian cancer (2007)
  • Author(s): Katabuchi H
  • Organizer: The International Ovarian Conference 2007
  • Place of Presentation: Hakone
• [Presentation] 不死化ヒト卵巣表層上皮細胞株を用いた上皮性卵巣癌の発癌機構の解明 (2007)
  • Author(s): 佐々木瑠美, 他
  • Organizer: 第66回日本癌学会
  • Place of Presentation: 横浜
• [Presentation] Human Ovarian Surface Epithelial Cell Lines : A New Tool to Investigate the Early Stages of Epithelial Ovarian Cancer (2006)
  • Author(s): Katabuchi H
  • Organizer: 6^<th> Sapporo International Symposium On Ovarian Function
  • Place of Presentation: Sapporo
  • Year and Date: 2006-08-06
• [Presentation] Human ovarian surface Epithelial cell lines: A new tool to investigate the early stage of epithelial ovarian cancer (2006)
  • Author(s): Katabuchi H
  • Organizer: The 11^<th> Taiwan joint cancer conference
  • Place of Presentation: Taiwan