Mechanism of chemoresistance by HDAC1-associating protein and development of molecular targeted therapy

2013 Fiscal Year Final Research Report

• Project/Area Number: 24650618
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Tumor biology
• Research Institution: Nagoya University
• Principal Investigator: TAKAHASHI Masahide 名古屋大学, 医学(系)研究科(研究院), 教授 (40183446)
• Co-Investigator(Kenkyū-buntansha): MURAKUMO Yoshiki 北里大学, 医学部, 教授 (40324438) ; KATO Takuya 名古屋大学, 医学系研究科, 助教 (00551970)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: HDAC1 / RET finger protein / 抗がん剤耐性 / 卵巣がん

Research Abstract

Resistance to platinum- and taxane-based chemotherapy is a major cause of treatment failure in ovarian cancer. Thus, it is necessary to develop a predictive marker and molecular target for overcoming drug resistance in ovarian cancer treatment. Using an in vitro model, we previously found that the RET finger protein (RFP) which is known as HDAC-associating protein, confers cancer cell resistance to anticancer drugs. In this study, we showed that RFP was expressed in 62% of ovarian cancer patients and its positivity significantly correlated with drug resistance. Depletion of RFP by RNA interference in ovarian cancer cell lines, SKOV3 and HEY, significantly increased carboplatin- or paclitaxel-induced apoptosis and resulted in reduced anticancer drug resistance. In a nude mouse tumor xenograft model, inoculated RFP-knockdown ovarian cancer cells exhibited lower carboplatin resistance than control cells. These findings suggest that RFP could be a candidate for a molecular-targeted agent.

Research Products

• [Journal Article] TRIM27/MTRF-B-dependent integrin beta1 expression defines leading cells in cancer cell collecitives (2014)
  • Author(s): Kato, T., Enomoto, A., Watanabe, T., Haga, H., Ishida, S., Kondo, Y., Furukawa, K., Urano, T., Mii, S., Weng, L., Takagishi, M., Asai, M., Asai, N., Kaibuchi, K., Murakumo, Y. and Takahashi, M.
  • Journal Title: Cell Rep Volume: (in press)
• [Journal Article] Suppression of REV7 enhances cisplatin sensitivity in ovarian clear cell carcinoma cells (2014)
  • Author(s): Niimi, K., Murakumo, Y., Watanabe, N., Kato, T., Mii, S., Enomoto, A., Asai, M., Asai, N., Yamamoto, E., Kajiyama, H., Shibata, K., Kikkawa, F., and Takahashi, M.
  • Journal Title: Cancer Sci Volume: 105 Pages: 545-552
• [Journal Article] The Rev7 subunit of DNA polymeraseζis essential for primordial germ cell maintenance in the mouse (2013)
  • Author(s): Watanabe, N., Mii, S., Asai, N., Asai, M., Niimi, K., Ushida, K., Kato, T., Enomoto, A., Ishii, H., Takahashi, M., and Murakumo, Y.
  • Journal Title: J. Biol. Chem Volume: 288 Pages: 10459-10471
• [Journal Article] Expression of RET finger protein predicts chemoresistance in epithelial ovarian cancer (2012)
  • Author(s): Horio, M., Kato, T., Mii, S., Enomoto, A., Asai, M., Asai, N., Murakumo, Y., Shibata, K., Kikkawa, F. and Takahashi, M.
  • Journal Title: Cancer Med Volume: 1 Pages: 218-229
• [Journal Article] RET finger protein expression is associated with prognosis in lung cancer with epidermal growth factor receptor mutations Pathol (2012)
  • Author(s): Iwakoshi, A., Murakumo, Y., Kato, T., Kitamura, A., Mii, S., Saito, S., Yatabe, Y. and Takahashi. M.
  • Journal Title: Int Volume: 62 Pages: 324-330
• [Journal Article] Ret finger protein inhibits muscle differentiation by modulating serum response factor and enhancer of polycomb 1 (2012)
  • Author(s): Kee, H. J., Kim, J-R, Joung, H., Choe, N., Lee, S. E., Eom, G. H., Kim, J. C., Geyer, S. H., Jijiwa, M., Kato, T., Kawai, K., Weninger, W. J., Seo, S. B., Nam, K-I., Jeong, M. H., Takahashi, M. and Kook, H.
  • Journal Title: Cell Death Differ Volume: 19 Pages: 121-131
• [Presentation] Roles of the Akt substrate Girdin in cancer progression and angiogenesis (2014)
  • Author(s): Takahashi, M., Enomoto, A. and Asai, N.
  • Organizer: International Symposium on Nanomedicine
  • Place of Presentation: Nagoya University, Nagoya
  • Year and Date: 20140113-14
• [Presentation] Roles of the Akt substrate Girdin in cancer progression and angiogenesis (2013)
  • Author(s): Takahashi, M., Enomoto, A. and Asai, N.
  • Organizer: Joint meeting of the Medical School of Nagoya University and the University of Adelaide
  • Place of Presentation: The University of Adelaide, Adelaide, Australia
  • Year and Date: 2013-05-27
• [Presentation] RET finger protein related to early cancer recurrence and potential therapeutic target in ovarian cancer (2012)
  • Author(s): Horio, M., Kato, T., Enomoto, A., Asai, N., Murakumo, Y., Shibata, K., Kikkawa, F. and Takahashi, M.
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: ロイトン札幌、札幌市
  • Year and Date: 20120919-21
• [Remarks]
  • URL: http://www.med.nagoya-u.ac.jp/patho2/