Studies on the epigenetic regulations in neoplastic diseases of animals

• 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
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 獣医学 / 腫瘍 / エピジェネティクス / 動物 / エピジェネティックス

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: Research in Veterinary Science Volume: 97 Issue: 1 Pages: 60-63
  • DOI: 10.1016/j.rvsc.2014.04.008
  • Peer Reviewed
• [Journal Article] Epigenetic regulation of the ABCBl gene in drug-sensitive and drug-resistant lymphoid tumour cell lines obtained from canine patients (2014)
  • Author(s): Tomiyasu H, Goto-Koshino Y, Fujino Y, Ohno K, Tsujimoto H.
  • Journal Title: Vet J Volume: 199(1) Issue: 1 Pages: 103-109
  • DOI: 10.1016/j.tvjl.2013.10.022
  • Peer Reviewed
• [Journal Article] Prognostic significance of the expression levels of the p16, p15, and p14genes 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, Tsujimoto H.
  • Journal Title: Vet J Volume: 199(2) Issue: 2 Pages: 236-244
  • DOI: 10.1016/j.tvjl.2013.11.004
  • Peer Reviewed
• [Journal Article] Simultaneous Inactivation of the <i>p16, p15</i> and <i>p14</i> 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, Tsujimoto H.
  • Journal Title: Journal of Veterinary Medical Science Volume: 75 Issue: 6 Pages: 733-742
  • DOI: 10.1292/jvms.12-0351
  • NAID: 130003362118
  • ISSN: 0916-7250, 1347-7439
  • Peer Reviewed
• [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: Journal of Veterinary Medical Science Volume: 75 Issue: 4 Pages: 467-474
  • DOI: 10.1292/jvms.12-0448
  • NAID: 130002502194
  • ISSN: 0916-7250, 1347-7439
  • Peer Reviewed
• [Journal Article] The prognostic significance of minimal residual disease in the early phases of chemotherapy in dogs with high-grade B-cell lymphoma (2013)
  • Author(s): Sato, M., Yamazaki, J., Goto-Koshino, Y., Takahashi, M., Fujino, Y., Ohno, K. and Tsujimoto, H
  • Journal Title: Vet. J Volume: 195 Issue: 3 Pages: 319-324
  • DOI: 10.1016/j.tvjl.2012.07.013
  • Peer Reviewed
• [Journal Article] Analyses on Activation of NF-&kappa;B and Effect of Bortezomib in Canine Neoplastic Lymphoid Cell Lines (2013)
  • Author(s): Kojima K, Fujino Y, Goto-Koshino Y, Ohno K, Tsujimoto H.
  • Journal Title: Journal of Veterinary Medical Science Volume: 75 Issue: 6 Pages: 727-731
  • DOI: 10.1292/jvms.12-0168
  • NAID: 130003362111
  • ISSN: 0916-7250, 1347-7439
  • Peer Reviewed
• [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. (2012)
  • Author(s): Tomiyasu H, Watanabe M, Goto-Koshino Y, Fujino Y, Ohno K, Sugano S, Tsujimoto H.
  • Journal Title: Leuk Lymphoma Volume: (Epub ahead of print) Issue: 6 Pages: 1309-1315
  • DOI: 10.3109/10428194.2012.751529
  • Peer Reviewed
• [Presentation] 犬の辺縁帯リンパ腫(marginal zone lymphoma) 9頭における臨床的・臨床病理学的特徴 (2014)
  • Author(s): 水田賢司, 高橋雅, 藤野泰人, 日吉沙綾, 福島建次郎, 金本英之, 大野耕一, 坪井誠也, 内田和幸, 辻本元
  • Organizer: 第10回日本獣医がん学会
  • Place of Presentation: 大阪
• [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
• [Presentation] GeneScanning analysis of clonal antigen receptor gene rearrangement in canine intestinal endoscopic biopsy specimens (2013)
  • Author(s): S. Hiyoshi, K. Uchida, K. Nakashima, K. Fukushima, H. Kanemoto, Y. Goto, Y. Fujino, K. Ohno, H. Tsujimoto
  • Organizer: The Asian Meeting of Animal Medicine Specialties (AMAMS)
  • Place of Presentation: Bogor, Indonesia
• [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 Meeting 2013
  • Place of Presentation: Minneapolis, Minnesota
• [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: パシフィコ横浜（神奈川県）
• [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: パシフィコ横浜（神奈川県）
• [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: パシフィコ横浜（神奈川県）