Studies on the epigenetic regulations in neoplastic diseases of animals

2013 Fiscal Year Final Research Report

• Project/Area Number: 24658265
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Clinical veterinary science
• Research Institution: The University of Tokyo
• Principal Investigator: TSUJIMOTO Hajime 東京大学, 農学生命科学研究科, 教授 (60163804)
• Co-Investigator(Renkei-kenkyūsha): SHIOTA Kunio 東京大学, 大学院農学生命科学研究科, 教授 (80196352)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: 獣医学 / 腫瘍 / エピジェネティクス

Research Abstract

Expressions of p16, p15, and p14 genes encoding CDK inhibitors (proteins that regulates cell cycle) and ABCB1 gene encoding one of the ABCD transporters (proteins that efflux drugs etc. from cells) were examined in canine lymphoma cells. Suppression of the expression of these genes via epigenetic regulations such as DNA methylation and histone H3 deacetylation was detected in a proportion of canine lymphoma cases. Moreover, treatment with epigenetic drugs to inhibit such regulations could restore their gene expression levels. The present study disclosed an important role of epigenetic regulation on the pathobiology of neoplastic diseases in animals.

Research Products

• [Journal Article] Inhibition of p16 tumor suppressor gene expression via promoter hypermethylation in canine lymphoid tumor cells (2014)
  • Author(s): Fujiwara-Igarashi, A., Goto-Koshino, Y., Mochizuki, H., Sato, M., Fujino, Y., Ohno, K. and Tsujimoto, H.
  • Journal Title: Res. Vet. Sci Volume: (Epub ahead of print)
  • DOI: 10.1016/j.rvsc.2014.04.008
• [Journal Article] Epigenetic regulation of the ABCB1 gene in drug-sensitive and drug-resistant lymphoid tumor cell lines obtained from canine patients (2014)
  • Author(s): Tomiyasu, H., Goto-Koshino Y., Fujino, Y., Ohno, K. and Tsujimoto, H.
  • Journal Title: Vet. J Volume: 199 Pages: 103-109
  • DOI: 10.1016/j.tvjl.2013.10.022
• [Journal Article] Prognostic significance of the expression levels of the p16, p15, and p14 genes in dogs with high-grade lymphoma (2014)
  • Author(s): Fujiwara-Igarashi, A., Goto-Koshino, Y., Sato, M., Maeda, S., Igarashi, H., Takahashi, M., Fujino, Y., Ohno, K. and Tsujimoto, H.
  • Journal Title: Vet. J Volume: 199 Pages: 236-244
  • DOI: 10.1016/j.tvjl.2013.11.004
• [Journal Article] Simultaneous inactivation of the p16, p15, and p14 genes encoding cyclin-dependent kinase inhibitors in canine T-lymphoid tumor cells (2013)
  • Author(s): Fujiwara-Igarashi, A., Goto-Koshino, Y., Mochizuki, H., Maeda, S., Fujino, Y., Ohno, K. and Tsujimoto, H.
  • Journal Title: J. Vet. Med. Sci Volume: 75 Pages: 733-742
  • DOI: 10.1292/jvms.12-0351
• [Journal Article] Regulation of the expression of ABCB1 and LRP genes by MAPK/ERK pathway and its role in the generation of side population cells in canine lymphoma cell lines (2013)
  • Author(s): Tomiyasu, H., Watanabe, M., Goto-Koshino, Y., Fujino, Y., Ohno, K., Sugano, S. and Tsujimoto, H.
  • Journal Title: Leuk. Lymphoma Volume: 54 Pages: 1309-1315
  • DOI: 10.3109/10428194.2012.751529
• [Journal Article] Establishment of five canine lymphoma cell lines and tumor formation in a xenotransplantation model (2013)
  • Author(s): Umeki, S., Ema, Y., Suzuki, R., Kubo, M., Hayashi, T., Okamura, Y., Yamazaki, J., Tsujimoto, H., Tani, K., Hiraoka, H., Okuda, M. and Mizuno, T.
  • Journal Title: J. Vet Med. Sci Volume: 75 Pages: 467-474
  • DOI: 10.1292/jvms.12-0448
• [Presentation] GeneScanning analysis of antigen receptor gene rearrangement in the intestinal endoscopeic biopsy specimens and its application to the diagnosis of small cell lymphoma in dogs (2013)
  • Author(s): Hiyoshi, S., Uchida, K., Nakashima, K., Fukushima, K., Kanemoto, H., Goto, Y., Fujino, Y., Ohno, K. and Tsujimoto, H.
  • Organizer: The Asian Meeting of Animal Medicine Specialties (AMAMS) 2013
  • Place of Presentation: ボゴール,インドネシア
  • Year and Date: 2013-12-14
• [Presentation] Modulation of the expression of ABCB1 and LRP genes by perifosine in canine lymphoma cell lines (2013)
  • Author(s): Tomiyasu, H., Goto-Koshino, Y., Fujino, Y., Ohno, K. and Tsujimoto, H.
  • Organizer: Veterinary Cancer Society (VCS) Annual Meeting 2013
  • Place of Presentation: ミネアポリス、米国
  • Year and Date: 2013-10-19
• [Presentation] 犬リンパ腫症例において発現変動を示す血清中microRNAの同定 (2013)
  • Author(s): 藤原亜紀、水谷格之、五十嵐寛高、後藤裕子、高橋雅、藤野泰人、大野耕一、佐々木典康、辻本元
  • Organizer: 第9回日本獣医内科学アカデミー学術大会
  • Place of Presentation: 横浜
  • Year and Date: 2013-02-23
• [Presentation] 犬のリンパ系腫瘍細胞株におけるABCB1遺伝子のDNAメチル化およびヒストンアセチル化による発現制御に関する検討 (2013)
  • Author(s): 富安博隆、後藤裕子、藤野泰人、大野耕一、辻本元
  • Organizer: 第9回日本獣医内科学アカデミー学術大会
  • Place of Presentation: 横浜
  • Year and Date: 2013-02-23
• [Presentation] 犬の多中心型高悪性度リンパ腫症例におけるABCB1遺伝子のDNAメチル化状態の解析 (2013)
  • Author(s): 富安博隆、後藤裕子、藤野泰人、大野耕一、辻本元
  • Organizer: 第9回日本獣医内科学アカデミー学術大会
  • Place of Presentation: 横浜
  • Year and Date: 2013-02-23