Advanced research on cancer

2004 Fiscal Year Final Research Report Summary

• Project/Area Number: 11182101
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: The University of Tokyo
• Principal Investigator: TANIGUCHI Tadatsugu The University of Tokyo, Graduate School of Medicine, Professor, 大学院医学系研究科, 教授 (50133616)
• Co-Investigator(Kenkyū-buntansha): NISHIDA Eisuke University of Kyoto, Graduate School of Biostudies, Professor, 大学院生命科学研究科, 教授 (60143369) ; TSUKITA Shoichiro University of Kyoto, Graduate School of Medicine, Professor, 医学研究科, 教授 (50155347) ; NISHIKAWA Shinichi The Institute of Physical and chemical Research, Laboratory for Stem Cell Biology, Group Director, 発生・再生科学総合研究センター, グループディレクター(研究職) (60127115) ; MIYAZONO Kohei The University of Tokyo, Graduate School of Medicine, Professor, 大学院医学系研究科, 教授 (90209908) ; NAGATA Shigekazu Osaka University, Graduate School of Frontier Biosciences, Professor, 大学院生命機能研究科, 教授 (70114428)
• Project Period (FY): 1999 – 2004
• Keywords: advanced research / cell adhesion / tumore supressor gene / signal transduction / apoptosis / Cytokine / immune response / anticancer agent

Research Abstract

This priority area, termed "Advanced research on cancer", is aimed at seeking cutting-edge cancer research by incorporating new technologies, disciplines and newly developing fields. In the past five years, much of the new insights have been gained about the mechanisms of oncogenic cell signaling and its suppression, particularly on the role of interferons and TGF-β, both of which function as negative regulator of cell growth. It also became possible to visualize behaviors of oncogene products in living cells and this is a new, important step to our understanding of cell transformation. New molecules have also been identified, which regulate cell adhesion and movement, and their functional analyses have been pursued; these include Claudins and WAVEs and these studies offered new insights in infiltration and metastasis of cancer cells. In addition, much progress has been made in understanding the mechanisms of apoptosis of cancerous cells and the clearance of such dying cells. It is particularly worth mentioning that one of the research project in this priority area spawned a new translational research project, that is, identification of HB-EGF as the target of ovarian cancers and application of CRM197, a mutant form of diphtheria toxin that inhibits HB-EGF, for therapy of this form of cancer. Overall, these achievements are represented in over several thousands of published papers, many of which appeared in journals such as Nature. Many collaborations with industries have been in progress with the aim of developing new drugs for cancer.

Research Products

• [Journal Article] Integral role of IRF-5 in the gene induction programme activated by Toll-like receptors. (2005)
  • Author(s): Takaoka A., Yanai H., Kondo S., Duncan G., Negishi H., Mizutani T., Kano S., Honda K., Ohba Y., Mak T.M., Taniguchi T.
  • Journal Title: Nature (On line)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] A high level of endothelial cell-specific gene expression by a combination of 5' flanking region and 5' half of the first intron of VE-cadherin gene. (2005)
  • Author(s): Hisatsune H, Matsumura K, Ogawa M, Uemura A, Kondo K, Yamashita J, Katsuta H, Nishikawa S, Chiba T, Nishikawa SI
  • Journal Title: Blood (印刷中)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Integral role of IRF-5 in the gene induction programme activated by Toll-like receptors. (2005)
  • Author(s): Takaoka A., Yanai H., Kondo S., Duncan G., Negishi H., Mizutani T., Kano S., Honda K., Ohba Y., Mak T.M., Taniguchi T.
  • Journal Title: Nature On line
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] A high level of endothelial cell-specific gene expression by a combination of 5' flanking region and 5' half of the first intron of VE-cadherin gene. (2005)
  • Author(s): Hisatsune H, Matsumura K, Ogawa M, Uemura A, Kondo K, Yamashita J, Katsuta H, Nishikawa S, Chiba T, Nishikawa SI
  • Journal Title: Blood (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Sef is a spatial regulator for Ras/MAP kinase signaling. (2004)
  • Author(s): Torii, S., Kusakabe, M., Yamamoto, T., Maekawa, M., Nishida.E.
  • Journal Title: Dev. Cell 7 Pages: 33-44
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Establishment and characterization of cultured epithelial cells lacking expression of ZO-1. (2004)
  • Author(s): Umeda, K., Matsui, T., Nakayama, M., Furuse, K., Sasaki, H., Furuse, M., Tsukita.Sh.
  • Journal Title: J.Biol.Chem. 279 Pages: 44785-44794
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Roles for the MH2 domain of Smad7 in the specific inhibition of transforming growth factor- β superfamily signaling. (2004)
  • Author(s): Mochizuki, T., Miyazaki, H., Hara, T., Furuya, T., Imamura, T., Watabe, T., Miyazono, K.
  • Journal Title: J. Biol. Chem. 279 Pages: 31568-31574
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Autoimmune disease and impaired uptake of apoptotic cells in MFG-E8-deficient mice. (2004)
  • Author(s): Hanayama, R., Tanaka, M., Miyasaka, K., Aozasa, K., Koike, M., Uchiyama.Y., Nagata.S.
  • Journal Title: Science 304 Pages: 1147-1150
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Sef is a spatial regulator for Ras/MAP kinase signaling. (2004)
  • Author(s): Torii, S., Kusakabe, M., Yamamoto, T., Maekawa, M., Nishida, E.
  • Journal Title: Dev. Cell 7 Pages: 33-44
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Establishment and characterization of cultured epithelial cells lacking expression of ZO-1. (2004)
  • Author(s): Umeda, K., Matsui, T., Nakayama, M., Furuse, K., Sasaki, H., Furuse, M., Tsukita, Sh.
  • Journal Title: J. Biol. Chem. 279 Pages: 44785-44794
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Roles for the MH2 domain of Smad7 in the specific inhibition of transforming growth factor-β superfamily signaling. (2004)
  • Author(s): Mochizuki, T., Miyazaki, H., Hara, T., Furuya, T., Imamura, T., Watabe, T., Miyazono, K.
  • Journal Title: J. Biol. Chem 279 Pages: 31568-31574
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Autoimmune disease and impaired uptake of apoptotic cells in MFG-E8-deficient mice. (2004)
  • Author(s): Hanayama, R., Tanaka, M., Miyasaka, K., Aozasa, K., Koike, M.Uchiyama, Y., Nagata, S.
  • Journal Title: Science 304 Pages: 1147-1150
  • Description: 「研究成果報告書概要(欧文)」より