A fundamental research for developing ubiquitin-targeted cancer therapies utilizing vesicular transport related molecules Hrs knocked-out mice.

• Project/Area Number: 20390428
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Tohoku University
• Principal Investigator: YAEGASHI Nobuo Tohoku University, 大学院・医学系研究科, 教授 (00241597)
• Co-Investigator(Kenkyū-buntansha): TOYOSHIMA Masafumi 東北大学, 大学院・医学系研究科, 非常勤講師 (70451581) ; SUGAMURA Kazuo 宮城県立がんセンター(研究所), 免疫学部, 総長 (20117360)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥19,370,000 (Direct Cost: ¥14,900,000、Indirect Cost: ¥4,470,000); Fiscal Year 2010: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2009: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2008: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000)
• Keywords: Hrs / 癌 / マウス / ユビキチン / ライソソーム / ノックアウトマウス / 小胞体輸送

Research Abstract

Defect of vesicle transport related molecule Hrs diminishes the expression of c-Myc. There are some reports concerning the relationship between c-Myc overexpression and poor prognosis of cancer patients. We attempted to identify new therapeutic target utilizing c-Myc overexpression as a biomarker. We used a siRNA library consists of 3500 druggable genome for a screening, and selected Casein Kinase 1 epsilon as a new target. We also showed IC261, a specific inhibitor of Casein Kinase 1 epsilon has therapeutic effects in mouse ovarian cancer model.

Research Products

• [Journal Article] Inhibitory effect of curcumin on uterine leiomyoma cell proliferation. (2011)
  • Author(s): Tsuiji K, Takeda T, Li B, Wakabayashi A, Kondo A, Kimura T, Yaegashi N.
  • Journal Title: Gynecol Endocrinol. (accepted)
  • Peer Reviewed
• [Journal Article] Relationship between ABCF2 expression and response to chemotherapy or prognosis in clear cell adenocarcinoma of the ovary. (2010)
  • Author(s): Tsuda H, Ito K, Yaegashi N, Hirasawa A, Sudo T, Kita T, Terai Y, Kigawa J, Sugiyama T, Aoki D.
  • Journal Title: Int J Gynecol Cancer. 20(5) Pages: 794-797
  • Peer Reviewed
• [Journal Article] Steroid and Xenobiotic Receptor (SXR) as a possible prognostic marker in epithelial ovarian cancer. (2010)
  • Author(s): Yue X, Akahira J, Utsunomiya H, Miki Y, Takahashi N, Niikura H, Ito K, Sasano H, Okamura K, Yaegashi N.
  • Journal Title: Pathol Int. 60(5) Pages: 400-406
  • NAID: 10029331942
  • Peer Reviewed
• [Journal Article] Differential Expression of Hypoxia-Inducible Protein 2 Among Different Histological Types of Epithelial Ovarian Cancer and in Clear Cell. (2010)
  • Author(s): Nishimura S, Tsuda H, Ito K, Takano M, Terai Y, Jobo T, Kigawa J, Sugiyama T, Yaegashi N, Aoki D.
  • Journal Title: Int J Gynecol Cancer. 20 Pages: 220-226
  • Peer Reviewed
• [Journal Article] Relationship between ABCF2 expression and response to chemotherapy or prognosis in clear cell adenocarcinoma of the ovary. (2010)
  • Author(s): Tsuda H, Ito K, Yaegashi N, Hirasawa A, Sudo T, Kits T, Terai Y, Kigawa J, Sugiyama T, Aoki D.
  • Journal Title: Int J Gynecol Cancer Volume: 20(5) Pages: 794-797
  • Peer Reviewed
• [Journal Article] Inhibitory effect of curcumin on uterine leiomyoma cell proliferation. (2010)
  • Author(s): Tsuiji K, Takeda T, Li B, Wakabayashi A, Kondo A, Kimura T, Yaegashi N.
  • Journal Title: Gynecol Endocrinol
  • Peer Reviewed
• [Journal Article] Steroid and Xenobiotic Receptor (SXR) as a possible prognostic marker in epithelial ovarian cancer. (2010)
  • Author(s): Yue X, Akahira J, Utsunomiya H, Miki Y, Takahashi N, Niikura H, Ito K, Sasano H, Okamura K, Yaegashi N.
  • Journal Title: Pathol Int. Volume: 60(5) Pages: 400-406
  • NAID: 10029331942
  • Peer Reviewed
• [Journal Article] Differential Expression of Hypoxia-Inducible Protein 2 Among Different Histological Types of Epithelial Ovarian Cancer and in Clear Cell. (2010)
  • Author(s): Nishimura S, Tsuda H, Ito K, Takano M, Terai Y, Jobo T, Kigawa J, Sugiyama T, Yaegashi N, Aoki D
  • Journal Title: Int J Gynecol Cancer 20 Pages: 220-226
  • Peer Reviewed
• [Journal Article] The impact of complete surgical staging upon survival in early-stage ovarian clear cell carcinoma : a multi-institutional retrospective study. (2009)
  • Author(s): Takano M, Sugiyama T, Yaegashi N, Suzuki M, Tsuda H, Sagae S, Udagawa Y, Kuzuya K, Kigawa J, Takeuchi S, Tsuda H, Moriya T, Kikuchi Y.
  • Journal Title: International Journal of Gynecologic Cancer. 19 Pages: 1353-1357
  • Peer Reviewed
• [Journal Article] Generation of a syngeneic mouse model to study the intraperitoneal metastasis of ovarian cancer with in vivo luciferase imaging. (2009)
  • Author(s): Toyoshima M, Tanaka Y, Matumoto M, Yamazaki M, Nagase S, Sugamura K, Yaegashi N.
  • Journal Title: Luminescence. 24 Pages: 324-331
  • Peer Reviewed
• [Journal Article] Endometrioid uterine cancer: histopathological risk factors of local and distant recurrence. (2009)
  • Author(s): Fujimoto T, Nanjyo H, Fukuda J, Nakamura A, Mizunuma H, Yaegashi N, Sugiyama T, Kurachi H, Sato A, Tanaka T.
  • Journal Title: Gynecol Oncol. 112 Pages: 342-347
  • Peer Reviewed
• [Journal Article] The impact of complete surgical staging upon survival in early-stage ovarian clear cell carcinoma : a multi-institutional retrospective study. (2009)
  • Author(s): Takano M, Sugiyama T, Yaegashi N, Suzuki M, Tsuda H, Sagae S, Udagawa Y, Kuzuya K, Kigawa J, Takeuchi S, Tsuda H, Moriya T, Kikuchi Y
  • Journal Title: International Journal of Gynecologic Cancer 19 Pages: 1353-1357
  • Peer Reviewed
• [Journal Article] Generation of a syngeneic mouse model to study the intraperitoneal metastasis of ovarian cancer with in vivo luciferase imaging. (2009)
  • Author(s): Toyoshima M, Tanaka Y, Matumoto M, Yamazaki M, Nagase S, Sugamura K, Yaegashi N
  • Journal Title: Luminescence 24 Pages: 324-331
  • Peer Reviewed
• [Journal Article] Endometrioid uterine cancer : histopathological risk factors of local and distant recurrence (2009)
  • Author(s): Fujimoto T
  • Journal Title: Gynecol Oncol. 112 Pages: 342-347
  • Peer Reviewed
• [Journal Article] Loss of hrs in the central nervous system causes accumulation of ubiquitinated proteins and neurodegeneration. (2008)
  • Author(s): Tamai K, Toyoshima M, Tanaka N, Yamamoto N, Owada Y, Kiyonari H, Murata K, Ueno Y, Ono M, Shimosegawa T, Yaegashi N, Watanabe M, Sugamura K.
  • Journal Title: Am J Pathol. 173 Pages: 1806-1817
  • Peer Reviewed
• [Journal Article] Estrogen signaling ability in human endometrial cancer through the cancer-stromal interaction. (2008)
  • Author(s): Matsumoto M, Yamaguchi Y, Seino Y, Hatakeyama A, Takei H, Niikura H, Ito K, Suzuki T, Sasano H, Yaegashi N, Hayashi S.
  • Journal Title: Endocr Relat Cancer. 15(2) Pages: 451-463
  • Peer Reviewed
• [Journal Article] Midkine and its clinical significance in endometrial carcinoma. (2008)
  • Author(s): Tanabe K, Matsumoto M, Ikematsu S, Nagase S, Hatakeyama A, Takano T, Niikura H, Ito K, Kadomatsu K, Hayashi S, Yaegashi N.
  • Journal Title: Cancer Sci. 99(6) Pages: 1125-1130
  • NAID: 10024007074
  • Peer Reviewed
• [Journal Article] Loss of hrs in the central nervous system causes accumulation of ubiquitinated proteins and neurodegeneration (2008)
  • Author(s): Tamai K
  • Journal Title: Am J Pathol. 173 Pages: 1806-1817
  • Peer Reviewed
• [Journal Article] Estrogen signaling ability in human endometrial cancer through the cancer-stromal interaction (2008)
  • Author(s): Matsumoto M
  • Journal Title: Endocr Relat Cancer 15(2) Pages: 451-63
  • Peer Reviewed
• [Journal Article] Midkine and its clinical significance in endometrial carcinoma (2008)
  • Author(s): Tanabe K
  • Journal Title: Cancer Sci. 99(6) Pages: 1125-30
  • Peer Reviewed
• [Presentation] Identification of Targeted Therapies for MYC-amplified Ovarian Cancers by Functional Genomics (2010)
  • Author(s): 豊島将文
  • Organizer: 第69回日本癌学会臓器別シンポジウム(招待講演)
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-23
• [Presentation] Identification of Targeted Therapies for MYC-amplified Ovarian Cancers by Functional Genomics (2010)
  • Author(s): 豊島将文
  • Organizer: 第69回日本癌学会臓器別シンポジウム
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-23
• [Remarks] ホームページ等なし