• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

2004 Fiscal Year Final Research Report Summary

IDENTIFICATION AND FUNCTIONAL ANALYSES OF THE GENES RELATED TO HEREDITARY BREAST CANCER

Research Project

Project/Area Number 12213141
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionTOKYO MEDICAL AND DENTAL UNIVERSITY (2002-2004)
Japanese Foundation For Cancer Research (2000-2001)

Principal Investigator

YOSHO Miki  TOKYO MEDICALAND DENTAL UNIVERSITY MEDICALRESEARCH INSTITUTE, PROFESSOR, 難治疾患研究所, 教授 (10281594)

Project Period (FY) 2000 – 2004
KeywordsHEREDITARY BREAST CANCER / BRCA1 / BRCA2 / DNA DAMAGE REPAIR / CYTOKINESIS / CYTOSKELETON / APOPTOSIS
Research Abstract

BRCA1 and BRCA2 were identified as a responsible gene of hereditary breast cancers, and presymptomatic diagnosis demonstrates big power clinically. It is thought that BRCA1 and BRCA2 are caretaker type antioncogenes which work to genome stabilization. Then, we focused on BRCA2, and tried to identify the molecules combined with the BRCA2 protein, and to elucidate the physiological function of BRCA2 based on the meaning of the signal transduction. It is thought that this research greatly contributes to the understanding of the meaning of the signal transduction borne by the target molecule, i. e., the mechanism of breast carcinogenesis.
We showed that two or more nuclear localization signals exist in C terminal of BRCA2, and nuclear export signals are among these. We presumed they functioned integrative and controlled subcellular localization of BRCA2. Moreover, it was shown clearly that Rad51 combines with BRCA2, and BRCA is participating in the double strand break repair of DNA. On the other hand, BRCA2 protein is combined with cytoskeletons, such as myosin, plectin, actinin, and γ-tubulin. BRCA2 is distributed in the nucleus and also around the nucleus toward the centrosome in the cell of G1-S, and colocalizing with γ-tubulin gradually in G2-M. It exists as phosphorylated protein around the chromosomes at M stage. From these results, it was supposed that subcellular localization of BRCA2 differed with each stage of cell cycle, and BRCA2 protein was carrying out the important work in cytokinesis. Furthermore, it identified that TRAF1 and Tax binding protein interacted with BRCA2, and a possibility that BRCA2 would control the apoptosis through NF-kappa B was shown. Taken together, BRCA2 is considered to have functions of DNA damage repair, cytokinesis regulation, and apoptosis control, and to function on homeostasis comprehensively.

  • Research Products

    (14 results)

All 2005 2004

All Journal Article (14 results)

  • [Journal Article] JNK phosphorylation of 14-3-3 regulates nuclear targeting of c-Ab1 in the apoptotic response to DNA damage.2005

    • Author(s)
      Yoshida, K.et al.
    • Journal Title

      Nat Cell Biol. 7

      Pages: 278-285

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] JNK phosphorylation of 14-3-3 regulates nuclear targeting of c-Abl In the apoptotic response to DNA damage.2005

    • Author(s)
      Yoshida, K., Yamaguchi, T., Natsume, T., Kufe, D., Miki Y.
    • Journal Title

      Nat Cell Biol. 7

      Pages: 278-285

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Role of BRCA1 and BRCA2 as regulators of DNA repair, transcription, and cell cycle in response to DNA damage.2004

    • Author(s)
      Yoshida, K.et al.
    • Journal Title

      Cancer Sci. 95

      Pages: 866-871

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Genome-wide gene-expression profiles of breast-cancer cells purified with laser microbeam microdissection : identification of genes associated with progression and metastasis.2004

    • Author(s)
      Nishidate, T.et al.
    • Journal Title

      Int J Oncol. 25

      Pages: 797-819

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Familial breast and ovarian cancers.2004

    • Author(s)
      Arai, M.et al.
    • Journal Title

      Int J Clin Oncol. 4

      Pages: 270-282

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Relatively common mutations of the Bloom syndrome gene in the Japanese population.2004

    • Author(s)
      Kaneko, H.et al.
    • Journal Title

      Int.J.Mol.Med. 14

      Pages: 439-442

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Gene expression patterns as marker for 5-year postoperative prognos is of primary breast cancers.2004

    • Author(s)
      Onda, M.et al.
    • Journal Title

      J.Cancer Res.Clin.Oncol 130

      Pages: 537-545

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Role of BRCA1 and BRCA2 as regulators of DNA repair, transcription, and cell cycle in response to DNA damage.2004

    • Author(s)
      Yoshida, K., Miki. Y.
    • Journal Title

      Cancer Sci. 95

      Pages: 866-871

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Genome-wide gene-expression profiles of breast-cancer cells purified with laser microbeam microdissection : identification of genes associated with progression and metastasis.2004

    • Author(s)
      Nishidate, T., Katagiri, T., Lin, M.L., Mano, Y., Miki.Y.Kasumi, F., Yoshimoto, M., Tsunoda, T., Hirata, K., Nakamura, Y.
    • Journal Title

      Int J Oncol. 25

      Pages: 797-819

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Familial breast and ovarian cancers.2004

    • Author(s)
      Arai, M., Utsunomiya, J., Miki.Y.
    • Journal Title

      Int J Clin Oncol. 4

      Pages: 270-282

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Relatively common mutations of the Bloom syndrome gene in the Japanese population.2004

    • Author(s)
      Kaneko, H., Isogai, K., Fukao, T., Matsui, E., Kasahara, K., Yachie, A., Seki, H., Koizumi, S., Arai, M., Utsunomiya, J., Miki.Y., Kondo, N.
    • Journal Title

      Int.J.Mol.Med. 14

      Pages: 439-442

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Gene expression patterns as marker for 5-year postoperative prognosis of primary breast cancers.2004

    • Author(s)
      Onda, M., Emi, M., Nagai, H., Nagahata, T., Tsumagari, K., Fujimoto, T., Akiyama, F., Sakamoto, G., Makita, M., Kasumi, F., Miki Y Tanaka, T., Tsunoda, T., Nakamura, Y.
    • Journal Title

      J.Cancer Res.Clin.Oncol. 130

      Pages: 537-545

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Expression profiling to predict postoperative prognosis for estrogen receptor-negative breast cancers by analysis of 25,344 genes on a cDNA microarray.2004

    • Author(s)
      Nagahata, T., Onda, M., Emi, M., Nagai, H., Tsumagari, K., Fujimoto, T., Hirano, A., Sato, T., Nishikawa, K., Akiyama, F., Sakamoto, G., Kasumi, F., Miki.Y..Tanaka, T., Tsunoda, T.
    • Journal Title

      Cancer Sci. 95

      Pages: 218-225

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Genotyping of single nucleotide polymorphism using model-based clustering.2004

    • Author(s)
      Fujisawa, H., Eguchi, S., Ushijima, M., Miyata, S., Miki.Y., Muto, T., Matsuura, M.
    • Journal Title

      Bioinformatics. 20

      Pages: 718-726

    • Description
      「研究成果報告書概要(欧文)」より

URL: 

Published: 2008-05-27  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi