Development of functional assays for tumor-related genes

2009 Fiscal Year Final Research Report

• Project/Area Number: 17015002
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Tohoku University
• Principal Investigator: ISHIOKA Chikashi Tohoku University, 加齢医学研究所, 教授 (60241577)
• Co-Investigator(Kenkyū-buntansha): KATO Shunsuke 東北大学, 加齢医学研究所, 准教授 (40312657) ; SHIMODAIRA Hideki 東北大学, 病院, 講師 (70373214) ; CHIBA Natuko 東北大学, 加齢医学研究所, 准教授 (50361192) ; SHIBATA Hiroyuki 秋田大学, 医学部, 教授 (50260071)
• Project Period (FY): 2005 – 2009
• Keywords: がん関連遺伝子 / がん抑制遺伝子

Research Abstract

Cancer contains multiple gene mutations. These mutations are often involved in carcinogenesis, tumor progression, invasion and metastasis, and also involved in individual cancer risk when these are hereditary transmitted. In this study, we have developed multiple functional assays to evaluate functional significance of mutations in various tumor-related genes and to predict prognosis of early breast cancer.

Research Products

• [Journal Article] Identification of breast tumor mutations in BRCA1 that abolish its function in homologous DNA recombination (2010)
  • Author(s): Ransburgh, D.J., Chiba, N., Ishioka, C., Toland, A.E., Parvin, J. D
  • Journal Title: Cancer Res 70 Pages: 988-95
  • Peer Reviewed
• [Journal Article] alphaB-crystallin: A novel p53-target gene required for p53-dependent apoptosis (2009)
  • Author(s): Watanabe, G., Kato, S., Nakata, H., Ishida, T., Ohuchi, N., Ishioka, C
  • Journal Title: Cancer Sci 100 Pages: 2368-2375
• [Journal Article] Newly synthesized curcumin analog has improved potential to prevent colorectal carcinogenesis in vivo (2009)
  • Author(s): Shibata, H., Yamakoshi, H., Sato, A., Ohori, H., Kakudo, Y., Kudo, C., Takahashi, Y., Watanabe, M., Takano, H., Ishioka, C., Noda, T., Iwabuchi, Y
  • Journal Title: Cancer Sci 100 Pages: 956-60
• [Journal Article] Determination of splice-site mutations in Lynch syndrome (hereditary non-polyposis colorectal cancer) patients using functional splicing assay (2009)
  • Author(s): Naruse, H., Ikawa, N., Yamaguchi, K., Nakamura, Y., Arai, M., Ishioka, C., Sugano, K., Tamura, K., Tomita, N., Matsubara, N., Yoshida, T., Moriya, Y., Furukawa, Y
  • Journal Title: Fam Cancer 8 Pages: 509-517
• [Journal Article] Rapid Recruitment of BRCA1 to DNA Double-Strand Breaks Is Dependent on Its Association with Ku80 (2008)
  • Author(s): Wei, L., Lan, L., Hong, Z., Yasui, A., Ishioka, C., Chiba, N
  • Journal Title: Mol Cell Biol 28 Pages: 7380-93
• [Journal Article] Prediction of breast cancer prognosis by gene expression profile of TP53 status (2008)
  • Author(s): Takahashi, S., Moriya, T., Ishida, T., Shibata, H., Sasano, H., Ohuchi, N., Ishioka, C
  • Journal Title: Cancer Sci 99 Pages: 324-32
• [Journal Article] Analysis of p53 mutation status in human cancer cell lines: a paradigm for cell line cross-contamination (2008)
  • Author(s): Berglind, H., Pawitan, Y., Kato, S., Ishioka, C., Soussi, T
  • Journal Title: Cancer Biol Ther 7 Pages: 699-708
• [Journal Article] Functional analysis of human MLH1 variants using yeast and in vitro mismatch repair assays (2007)
  • Author(s): Takahashi, M., Shimodaira, H., Andreutti-Zaugg, C., Iggo, R., Kolodner, R.D., Ishioka, C
  • Journal Title: Cancer Res 67 Pages: 4595-604
• [Journal Article] Alpha-catenin is essential in intestinal adenoma formation (2007)
  • Author(s): Shibata, H., Takano, H., Ito, M., Shioya, H., Hirota, M., Matsumoto, H., Kakudo, Y., Ishioka, C., Akiyama, T., Kanegae, Y., Saito, I., Noda, T
  • Journal Title: Proc Natl Acad Sci U S A 104 Pages: 18199-204
• [Journal Article] Impact of mutant p53 functional properties on TP53 mutation patterns and tumor phenotype: lessons from recent developments in the IARC TP53 database (2007)
  • Author(s): Petitjean, A., Mathe, E., Kato, S., Ishioka, C., Tavtigian, S.V., Hainaut, P., Olivier, M
  • Journal Title: Hum Mutat 28 Pages: 622-9
• [Journal Article] The screening of the second-site suppressor mutations of the common p53 mutants (2007)
  • Author(s): Otsuka, K., Kato, S., Kakudo, Y., Mashiko, S., Shibata, H., Ishioka, C
  • Journal Title: Int J Cancer 121 Pages: 559-66
• [Journal Article] MUT-TP53: a versatile matrix for TP53 mutation verification and publication (2006)
  • Author(s): Soussi, T., Rubio-Nevado, J.M., Ishioka, C
  • Journal Title: Hum Mutat 27 Pages: 1151-1154
• [Journal Article] Locus-specific mutation databases: pitfalls and good practice based on the p53 experience (2006)
  • Author(s): Soussi, T., Ishioka, C., Claustres, M., Beroud, C
  • Journal Title: Nat Rev Cancer 6 Pages: 83-90
• [Journal Article] Meta-analysis of the p53 Mutation Database for Mutant p53 Biological Activity Reveals a Methodologic Bias in Mutation Detection (2006)
  • Author(s): Soussi, T., Asselain, B., Hamroun, D., Kato, S., Ishioka, C., Claustres, M., Beroud, C
  • Journal Title: Clin Cancer Res 12 Pages: 62-69
• [Journal Article] The Clinical Value of Somatic TP53 Gene Mutations in 1, 794 Patients with Breast Cancer (2006)
  • Author(s): Olivier, M., Langerod, A., Carrieri, P., (other authors), Kato, S., Ishioka, C., Hainaut, P., Borresen-Dale, A
  • Journal Title: Clin Cancer Res 12 Pages: 1157-1167
• [Journal Article] Synthesis and biological analysis of new curcumin analogues bearing an enhanced potential for the medicinal treatment of cancer (2006)
  • Author(s): Ohori, H., Yamakoshi, H., Tomizawa, M., Shibuya, M., Kakudo, Y., Takahashi, A., Takahashi, S., Kato, S., Suzuki, T., Ishioka, C., Iwabuchi, Y., Shibata, H
  • Journal Title: Mol Cancer Ther 2006 5 Pages: 2563-2571
• [Journal Article] Predicting the Transactivation Activity of p53 Missense Mutants Using a Four-Body Potential Score Derived From Delaunay Tessellations (2006)
  • Author(s): Mathe, E., Olivier, M., Kato, S., Ishioka, C., Vaisman, I., Hainaut, P
  • Journal Title: Hum Mutat 27 Pages: 163-172
• [Journal Article] Computational approaches for predicting the biological effect of p53 missense mutations: a comparison of three sequence analysis based methods (2006)
  • Author(s): Mathe, E., Olivier, M., Kato, S., Ishioka, C., Hainaut, P., Tavtigian, S. V
  • Journal Title: Nucleic Acids Res 34 Pages: 1317-25
• [Journal Article] The UMD TP53 database and website: update and revisions (2006)
  • Author(s): Hamroun, D., Kato, S., Ishioka, C., Claustres, M., Beroud, C., Soussi, T
  • Journal Title: Hum Mutat 27 Pages: 14-20
• [Journal Article] Functional categories of TP53 mutation in colorectal cancer: results of an International Collaborative Study (2006)
  • Author(s): Iacopetta, B., Russo, A., Bazan, V., (other authors), Kato, S., Ishioka, C
  • Journal Title: Ann Oncol 17 Pages: 842-847
• [Journal Article] BRCA1/BARD1 ubiquitinate phosphorylated RNA polymerase II (2005)
  • Author(s): Starita, L.M., Horwitz, A.A., Keogh, M.C., Ishioka, C., Parvin, J.D., Chiba, N
  • Journal Title: J Biol Chem 280 Pages: 24498-505
• [Journal Article] Reassessment of the TP53 mutation database in human disease by data mining with a library of TP53 missense mutations (2005)
  • Author(s): Soussi, T., Kato, S., Levy, P.P., Ishioka, C
  • Journal Title: Hum Mutat 25 Pages: 6-17
• [Journal Article] The relationship among p53 oligomer formation, structure and transcriptional activity using a comprehensive missense mutation library (2005)
  • Author(s): Kawaguchi, T., Kato, S., Otsuka, K., Watanabe, G., Kumabe, T., Tominaga, T., Yoshimoto, T., Ishioka, C
  • Journal Title: Oncogene 24 Pages: 6976-81
• [Journal Article] Lack of correlation between p53-dependent transcriptional activity and the ability to induce apoptosis among 179 mutant p53s (2005)
  • Author(s): Kakudo, Y., Shibata, H., Otsuka, K., Kato, S., Ishioka, C
  • Journal Title: Cancer Res 65 Pages: 2108-14
• [Presentation] Cytoplasmically localized wild-type p53 and S121F super p53 still retains apoptosis inducible abilities (2009)
  • Author(s): Yasuda, K., Kato, S., Sakamoto, Y., Watanabe, G., Kakudo, Y., Ishioka, C.
  • Organizer: 2009 AACR Annual Meeting
  • Place of Presentation: Denver Colorado USA(Poster)
  • Year and Date: 2009-04-19
• [Presentation] 大腸癌薬物療法の進歩、日本の標準と国際標準の違いと将来 (2008)
  • Author(s): Ishioka, C
  • Organizer: 中日胃腸腫瘍総合治療学術シンポジウム
  • Place of Presentation: 北京・中日友好病院臨床研究所講学庁
  • Year and Date: 2008-11-06
• [Presentation] Domain-dependent accumulation of BRCA1 at the sites of DNA damage (2007)
  • Author(s): Chiba, N., Ishioka, C
  • Organizer: AACR-NCI-EORTC International conference Molecular targets and Cancer Therapeutics
  • Place of Presentation: San Francisco・U.S. A(poster)
  • Year and Date: 2007-10-23
• [Presentation] Functional evaluation of genetic variants in hereditary colon cancer predispose genes (2007)
  • Author(s): Shimodaira, H., Takahashi, M., Ishioka, C
  • Organizer: The 66th Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Yokohama・Pacifico-Yokohama(International Sesseions)
  • Year and Date: 2007-10-05
• [Presentation] αB crystallin is a novel p53-target gene and required for p53-dependent apoposis (2007)
  • Author(s): Watanabe, G., Kato, S., Ishioka, C
  • Organizer: The 98th American Association for Cancer Research Annual Meeting
  • Place of Presentation: Los Angeles USA(Minisymposium)
  • Year and Date: 2007-04-16
• [Presentation] Two cases of breast cancer responding to trastuzumab monotherapy.. Asia Pacific Medical Education Initiative (2007)
  • Author(s): Chiba, N., Yoshioka, T., Takahashi, S., Shibata, H., Kato, S., Shimodaira, H., Otsuka, K., Kakudo, Y., Takahashi, M., Yasuda, K., Sakamoto, Y., Ishioka, C
  • Organizer: 3rd Asia Pacific Workshop, Molecular targeted Therapy of Cancer
  • Place of Presentation: Shanghai China
  • Year and Date: 2007-03-10
• [Presentation] Evaluation of prognostic significance of TP53 expression signature in breast cancer (2006)
  • Author(s): Ishioka, C., Shibata, H., Takahashi, S
  • Organizer: The 11th International Congress of Metastasis Research Society Jointed with the 15th Annual Meetng of Japanese Association for Metastasis Research (Plenary Sessions)
  • Place of Presentation: Tokushima Japan
  • Year and Date: 2006-09-06
• [Presentation] Functional characterization of hMLH1 missense mutations using yeast and in vitro assays (2006)
  • Author(s): Takahashi, M., Shimodaira, H., Ishioka, C
  • Organizer: 11th International Congress of Human Genetics
  • Place of Presentation: Brisbane, Australia(poster session)
  • Year and Date: 2006-08-09
• [Presentation] Expression signature of p53 status (p53 signature) for the prediction of TP53 mutation and prognosis in breast cancer (2006)
  • Author(s): Ishioka, C., Takahashi, S
  • Organizer: 42nd American Society of Clinical Oncology Annual Meeting
  • Place of Presentation: Atlanta, GA(poster)
  • Year and Date: 2006-06-03
• [Presentation] Interaction site of the mismatch repair protein PMS2 with the proapoptotic protein p73 (2006)
  • Author(s): Shimodaira, H., Takahashi, M., Ishioka, C
  • Organizer: The 97th American Association for Cancer Research Annual Meeting
  • Place of Presentation: Washington, DC., USA(poster)
  • Year and Date: 2006-04-04
• [Presentation] Functional analysis of hMLH1 mutations using yeast and in vitro mismatch repair assays (2006)
  • Author(s): Takahashi, M., Shimodaira, H., Kanamaru, R., Ishioka, C
  • Organizer: The 97th American Association for Cancer Research Annual Meeting
  • Place of Presentation: Washington, DC., USA(poster)
  • Year and Date: 2006-04-03
• [Presentation] Analysis of relationship between p53-dependent transcriptional activity and its ability to induce apoptosis (2005)
  • Author(s): Kakudo, Y., Shibata, H., Otsuka, K., Kato, S., Ishioka, C
  • Organizer: The 96th American Association for Cancer Research Annual Meeting
  • Place of Presentation: Anaheim U.S. A(Poster Session)
  • Year and Date: 2005-04-19
• [Book] 入門腫瘍内科学(編集委員), 秋田弘俊, 石岡千加史, 田村和夫, 中川和彦, 原田実根, 南博信編 入門腫瘍内科学(直腸, 結腸癌) (2009)
  • Author(s): 秋田弘俊, 石岡千加史, 田村和夫, 中川和彦, 原田実根, 南博信
  • Total Pages: 148-154
  • Publisher: 篠原出版社
• [Book] がん分子標的治療薬開発におけるProof of concept日本がん分子標的治療学会, 曽根三郎, 鶴尾隆編 がん分子標的治療研究実践マニュアル (2009)
  • Author(s): 石岡千加史
  • Total Pages: 47-52
  • Publisher: 金芳堂
• [Book] 第5章テーラーメイド医療の未来がんの個性と個別化帯刀益夫, 佐竹正延編加齢医学エイジング・ファイン (2007)
  • Author(s): 石岡千加史
  • Total Pages: 244-257
  • Publisher: 東北大学出版
• [Book] A. プロテインキナーゼ阻害薬西條長宏編抗悪性腫瘍薬マニュアル (2007)
  • Author(s): 石岡千加史
  • Total Pages: 386-416
  • Publisher: 中外医学社
• [Book] 4. がん薬物療法の分子標的4)アポトーシス西條長宏編 癌治療の新たな試み新編III (2005)
  • Author(s): 石岡千加史
  • Total Pages: 164-175
  • Publisher: 医薬ジャーナル社
• [Patent(Industrial Property Rights)] がんの予後予測方法 (2009)
  • Inventor(s): 石岡千加史、高橋信
  • Industrial Property Rights Holder: 東北大学
  • Industrial Property Number: 特許権特許第4370409号
  • Filing Date: 2009-09-11
• [Patent(Industrial Property Rights)] ビス(アリールメチリデン)アセトン化合物、抗癌剤、発癌予防剤、Ki-Ras、ErbB2、c-Myc及びCyclinD1の発現抑制剤、β-カテニン分解剤並びにp53の発現増強剤 (2007)
  • Inventor(s): 岩淵好治、柴田浩行
  • Industrial Property Rights Holder: 東北大学
  • Industrial Property Number: 特許権WO 2007/000998 A1
  • Filing Date: 2007-01-04