Rehabilitation of cancer cells

• Project/Area Number: 25670196
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Experimental pathology
• Research Institution: Juntendo University
• Principal Investigator: HINO Okio 順天堂大学, 医学部, 教授 (90127910)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 癌 / 病理学 / 再生医療 / 遺伝子 / ips化 / Tsc遺伝子 / 遺伝学 / 初期化

Outline of Final Research Achievements

Eker rats have a germline mutation in tuberous sclerosis 2 gene (Tsc2). Heterozygous mutants develop renal cell carcinomas (RCCs) within one year after birth, whereas homozygous mutants are embryonic lethal. To explore new strategies for treatment of cancer using epigenetic modification, we started studies with reprogramming of Eker rat’s cancer cells as a model case. For that, we first tried to generate Tsc2-deficient ES cells (ESCs) and embryonic fibroblast-derived iPS cells (iPSCs) from Eker rat’s, and analyzed effects of Tsc2-deficiency on pluripotency. We are characterizing them in terms of stemness and pluripotency.

Research Products

• [Journal Article] Establishiment of Tsc2-deficient rat embryonic stem cells. (2015)
  • Author(s): Ito Y., Kawano H., Kanai F., Nakamura E., Tada N., Takai S., Horie S., Arai H., Kobayashi T. & Hino O.
  • Journal Title: Int. J. Oncology Volume: 46 Issue: 5 Pages: 1944-1952
  • DOI: 10.3892/ijo.2015.2913
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Rheb activation disrupts spine synapse formation through accumulation of syntenin in tuberous sclerosis complex (2015)
  • Author(s): Hiroko Sugiura, Shin Yasuda, Shutaro Katsurabayashi, Hiroyuki Kawano, Kentaro Endo, Kotaro Takasaki, Katsunori Iwasaki, Masumi Ichikawa, Toshiyuki Kobayashi, Okio Hino and Kanato Yamagata
  • Journal Title: Nature Communications Volume: 6 Issue: 1 Pages: 6842-6842
  • DOI: 10.1038/ncomms7842
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Transgenic expression of the N525S-tuberin variant in Tsc2 mutant (Eker) rats causes dominant embryonic lethality. (2014)
  • Author(s): Shiono M., Kobayashi T., Takahashi R., Ueda M., Ishikawa C. and Hino O.
  • Journal Title: Scientific Reports Volume: 4 Issue: 1 Pages: 5927-5927
  • DOI: 10.1038/srep05927
  • Peer Reviewed
• [Journal Article] Activation of Rheb, but not of mTORC1, impairs spine synapse morphogenesis in tuberous sclerosis complex. (2014)
  • Author(s): Yasuda S, Sugiura H, Katsurabayashi S, Shimada T, Tanaka H, Takasaki K, Iwasaki K, Kobayashi T, Hino O, Yamagata K.
  • Journal Title: Sci Rep. Volume: 4 Issue: 1 Pages: 5155-5155
  • DOI: 10.1038/srep05155
  • Peer Reviewed / Open Access
• [Journal Article] Rheb-syntenin interaction regulates dendritic spine formation in rodent models of tuberous sclerosis. (2014)
  • Author(s): 285. Sugiura H., Yasuda S., Katsurabayashi S., Oguri K., Tanaka H., Takasaki K., Iwasaki K., Kobayashi T., Hino O. and Yamagata K.
  • Journal Title: PNAS Volume: in press
  • Peer Reviewed
• [Journal Article] TSC1 controls distribution of actin fibers through its effect on function of Rho family of small GTPases and regulates cell migration and polarity (2013)
  • Author(s): Ohsawa M, Kobayashi T, Hino O, et al
  • Journal Title: PLoS One Volume: 8(1) Issue: 1 Pages: e54503-e54503
  • DOI: 10.1371/journal.pone.0054503
  • Peer Reviewed
• [Journal Article] Tuberin activates and controls the distribution of Rac1 via association with p62 and ubiquitin through the mTORC1 signaling pathway. (2013)
  • Author(s): Okura, H., Kobayashi, T., Koike, M., Ohsawa, M., Zhang, D., Arai, H., Uchiyama, Y., *Hino O
  • Journal Title: Int J Oncol Volume: 43 Issue: 2 Pages: 447-456
  • DOI: 10.3892/ijo.2013.1984
  • Peer Reviewed
• [Journal Article] Src plays a key role in ADAM28 expression in v-src-transformed epithelial cells and human carcinoma cells. (2013)
  • Author(s): Abe H., Mochizuki S., Ohara K., Ueno M., Ohiai H., Kitagawa Y., Hino O., Sato H. and Okada Y.
  • Journal Title: The American Journal of Pathology Volume: 183 Pages: 1667-1678
  • Peer Reviewed