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

Multifaceted analysis of molecular pathogenesis of human lung cancers

Research Project

Project/Area Number 12213163
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionNagoya University (2004)
Aichi Cancer Center Research Institute (2000-2003)

Principal Investigator

TAKAHASHI Takashi  Nagoya University, Div. of Mol. Carcinog., Professor, 大学院医学系研究科, 教授 (50231395)

Co-Investigator(Kenkyū-buntansha) YANAGISAWA Kiyoshi  Nagoya University, Div. of Mol.Carcinog., Res.Assoc., 大学院医学系研究科, 助手 (20372112)
TOMIDA Shuta  Aichi Cancer Center, Div. of Mol. Oncol., Researche, 分子腫瘍学部, 研究員 (10372111)
KONISHI Hiroyuki  Aichi. Cancer Center, Div of Mol. Oncol., Senior Res., 分子腫瘍学部, 主任研究員 (20344335)
YATABE Yasushi  Aichi Cancer Center, Div. of Mol. Oncol., Researcher, 分子腫瘍学部, 研究員 (90280809)
OSADA Hirotaka  Aichi Cancer Center, Div. of Mol. Oncol., Section Head, 分子腫瘍学部, 室長 (30204176)
MASUDA Akira  Aichi Cancer Center, Div. of Mol.Oncol., Senior Res., 分子腫瘍学部, 主任研究員 (50157202)
KOZAKI Kenichi  Aichi Cancer Center, Div of Mol. Oncol., Researcher, 分子腫瘍学部, 研究員 (50270715)
Project Period (FY) 2000 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥90,900,000 (Direct Cost: ¥90,900,000)
Fiscal Year 2004: ¥18,100,000 (Direct Cost: ¥18,100,000)
Fiscal Year 2003: ¥18,500,000 (Direct Cost: ¥18,500,000)
Fiscal Year 2002: ¥19,000,000 (Direct Cost: ¥19,000,000)
Fiscal Year 2001: ¥18,300,000 (Direct Cost: ¥18,300,000)
Fiscal Year 2000: ¥17,000,000 (Direct Cost: ¥17,000,000)
Keywordsmolecular oncology / lung cancer / expression profiling / microarray / bioinformatics / metastasis / checkpoint / 網羅的遺伝子発現解析 / バイオインフォマティクス / 転移 / 網羅的発現解析 / がん抑制遺伝子 / がん遺伝子 / 染色体不安定性 / 癌抑制遺伝子 / 分子疫学
Research Abstract

In this research project, multi faceted analyses were conducted in order to better understand the molecular pathogenesis of human lung cancers. Consequently, we have successfully obtained the following results.
(1) Expression profiling analysis of lung cancer specimens using the microarray technology revealed the presence of considerable heterogeneity and also allowed us to construct a highly accurate model for predicting 5-yr survival after potentially curative resection. Expression profiling at the protein level has also initiated during this period, which will be rigorously investigated in the next term of this research project.
(2) By comparing expression profiles of a highly metastatic and its parental human lung cancer cell lines established in our laboratory, various molecules related to inflammation and some other biological responses such as angiogenesis and proteasome-dependent degradation were suggested to be involved in the process of metastasis. Further, we also isolated novel genes related to metastasis including CLCP1 and LNMO1 and characterized their roles in metastasis.
(3) We found the presence of persistent chromosomal instability in lung cancers and an indirect role of p53 in activation in the acquisition of chromosomal instability phenotype. We also found a homozygous deletion of 14・3・3ε at 17p13.3,a site of frequent alleic losses in lung cancers. This finding led us to identify that 14-3-3ε may play a role in G2 check point response in lung cancers. In addition, we found requently impaired decatenation G2 checkpoint in lung cancers as well as frequent epigenetic silencing of CHFR, a gene implicated in the prophase checkpoint.

Report

(6 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (48 results)

All 2004 2003 2002 2001 2000 Other

All Journal Article (20 results) Patent(Industrial Property Rights) (4 results) Publications (24 results)

  • [Journal Article] Gene expression-based, individualized outcome prediction of surgically treated lung cancer patients.2004

    • Author(s)
      Tomida, S., et al.
    • Journal Title

      Oncogene 23

      Pages: 5360-5370

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival.2004

    • Author(s)
      Takamizawa, J., et al.
    • Journal Title

      Cancer Res. 64

      Pages: 3753-3760

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Identification of decatenation G2 checkpoint impairment independently of DNA damage G2 checkpoint in human lung cancer cell lines.2004

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

      Cancer Res. 64

      Pages: 4826-4832

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Gene expression-based, individualized outcome prediction of surgically treated lung cancer patients.2004

    • Author(s)
      Tomida S, Koshikawa K, Yatabe Y, Harano T, Ogura N, Mitsudomi T, Some M, Takahashi T, Osada H, Takahashi T.
    • Journal Title

      Oncogene 23

      Pages: 5360-5370

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival.2004

    • Author(s)
      Takamizawa J, Konishi H, Yanagisawa K, Tomida S, Osada T, Harano T, Yatabe Y, Nagino M, Nimura Y, Mitsudomi T, Takahashi T.
    • Journal Title

      Cancer Res. 64

      Pages: 3753-3760

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Identification of decatenation G2 checkpoint impairment independently of DNA damage G2 checkpoint in human lung cancer cell lines.2004

    • Author(s)
      Nakagawa T, Hayashita.Y, Maeno K, Masuda A, Sugito N, Osada H, Yanagisawa K, Ebi H, Shimokata K, Takahashi T.
    • Journal Title

      Cancer Res. 64

      Pages: 4826-4832

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Mutations of the epidermal growth factor receptor gene in lung cancer. biological and clinical implications.2004

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

      Cancer Res. 64

      Pages: 8819-8923

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Cellular property-associated expression of maspin controlled by promoter DNA methylation in normal lung and non-small cell lung cancers.2004

    • Author(s)
      Yatabe, Y., et al.
    • Journal Title

      Oncogene 23

      Pages: 4041-4029

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Reduced expression of class II HDAC genes are associated with poor prognosis in lung cancer patients.2004

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

      Int.J.Cancer 112

      Pages: 26-32

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Association between mitotic spindle checkpoint impairment and susceptibility to the induction of apoptosis by antimicrotubule agents in human lung cancers.2003

    • Author(s)
      Masuda, A., et al.
    • Journal Title

      Am. J. Pathol. 163

      Pages: 1106-1119

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Association between mitotic spindle checkpoint impairment and susceptibility to the induction of apoptosis by antimicrotubule agents in human lung cancers.2003

    • Author(s)
      Masuda, A., Maeno, K., Nakagawa, T.Saito, T., Takahashi T.
    • Journal Title

      Am. J. Pathol. 163

      Pages: 1106-1119

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Identification of frequent G2 checkpoint impairment and a homozygous deletion of 14-3-3ε at 17p13.3 in small cell lung cancers2002

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

      Cancer Res. 62

      Pages: 271-276

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Identification of frequent G2 checkpoint impairment and a homozygous deletion of 14-3-3e at 17pl3.3 in small cell lung cancers.2002

    • Author(s)
      Konishi H, Nakagawa T, Harano T, Mizuno K, Saito H, Masuda A, Matsuda H, Osada H, Takahashi T.
    • Journal Title

      Cancer Res. 62

      Pages: 271-276

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Aberrant hypermethylation of the CHFR prophase checkpoint gene in human lung cancers.2002

    • Author(s)
      Mizuno K, Osada H, Konishi H, Tatematsu Y, Fujii Y, Takahashi T.
    • Journal Title

      Oncogene 21

      Pages: 2328-2333

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Multi-faceted analyses of a highly metastatic human lung cancer cell line NCI-H460-LNM35 suggest mimicry of inflammatory cells in metastasis2001

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

      Oncogene 20

      Pages: 4228-4234

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Multi-faceted analyses of a highly metastatic human lung cancer cell line NCI-H460-LNM35 suggest mimicry of inflammatory cells in metastasis.2001

    • Author(s)
      Kozaki K, Koshikawa K, Tatematsu Y, Miyaishi O, Saito H, Hida. T, Osada, H, Takahashi T.
    • Journal Title

      Oncogene 20

      Pages: 4228-4234

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Persistent increase in chromosome insta.bility in lung cancer : possible indirect involvement of p53 inactivation.2001

    • Author(s)
      Haruki N, Harano T, Masuda A, Kiyono T, Tatematsu Y, Shimizu S, Mitsudomi T, Konishi H, Osada H, Fujii Y, Takahashi T.
    • Journal Title

      Am.J.Pathol. 159

      Pages: 1345-1352

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Association between the dopamine D2 receptor A21A2 genotype and smoking behavior in the Japanese.2001

    • Author(s)
      Yoshida K, Hamajima N, Kozaki K, Saito H, Maeno K, Sugiura T, Ookuma K, Takahashi T.
    • Journal Title

      Cancer Epidemiol., Biomark., & Prev. 10

      Pages: 403-405

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] In vivo selected human lung cancer cell line NCI-H460-LNM35 consistently exhibits lymphogenous metastasis via both subcutaneous and orthotopic propagation.2000

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

      Cancer Res. 60

      Pages: 2535-2540

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] In vivo selected human lung cancer cell line NCI-H460-LNM35 consistently exhibits lymphogenous metastasis via both subcutaneous and orthotopic propagation.2000

    • Author(s)
      Kozaki K, Miyaishi O, Tsukamoto T, Tatematsu Y, Hida T, Takahashi T, Takahashi T.
    • Journal Title

      Cancer Res. 60

      Pages: 2535-2540

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Patent(Industrial Property Rights)] miRNAを用いた癌の予後判定方法、癌の遺伝子治療ベクター及び癌治療2004

    • Inventor(s)
      高橋 隆
    • Industrial Property Rights Holder
      愛知県
    • Industrial Property Number
      2004-002307
    • Filing Date
      2004-01-07
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Patent(Industrial Property Rights)] 肺癌治療剤2004

    • Inventor(s)
      高橋 隆 他2名
    • Industrial Property Rights Holder
      愛知県
    • Industrial Property Number
      2004-288979
    • Filing Date
      2004-09-30
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Patent(Industrial Property Rights)] 肺癌治療剤2004

    • Inventor(s)
      長田 啓隆, 高橋 隆, 谷田部 恭
    • Industrial Property Rights Holder
      愛知県
    • Industrial Property Number
      2004-288979
    • Filing Date
      2004-09-30
    • Related Report
      2004 Annual Research Report
  • [Patent(Industrial Property Rights)] 肺癌組織中の遺伝子発現強度を識別する方法2003

    • Inventor(s)
      高橋 隆 他5名
    • Industrial Property Rights Holder
      愛知県 他1社
    • Industrial Property Number
      2003-415119
    • Filing Date
      2003-12-12
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Tomida, S., et al.: "Gene expression-based, individualized outcome prediction of surgically treated lung cancer patients."Oncogene. (in press).

    • Related Report
      2003 Annual Research Report
  • [Publications] Masuda, A, et al.: "Association between mitotic spindle checkpoint impairment and susceptibility to the induction of apoptosis by antimicrotubule agents in human lung cancers."Am.J.Pathol.. 163. 1106-1119 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Konishi, H., et al.: "Detailed characterization of a homozygously deleted region corresponding to a candidate tumor suppressor locus at distal 17p13.3 in human lung cancer."Oncogene. 22. 1892-1905 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yatabe, Y., et al.: "Cellular property-associated expression of maspin controlled by promoter DNA methylation in normal lung and non-small cell lung cancers."Oncogene. (in press).

    • Related Report
      2003 Annual Research Report
  • [Publications] Osada, H., et al.: "Reduced expression of class II HDAC genes are associated with poor prognosis in lung cancer patients"Int.J.Cancer. (in press).

    • Related Report
      2003 Annual Research Report
  • [Publications] Endoh, S., et al.: "Prognostic model of pulmonary adenocarcinoma by expression profiling of eight genes as determined by quantitative real-time RT-PCR."J.Clin.Oncol.. 22. 811-819 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Konishi, H., et al.: "Identification of frequent G2 checkpoint impairment and a homozygous deletion of 14-3-3εat 17p13.3 in small cell lung cancers"Cancer Research. 62. 271-276 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] He, Y., et al.: "Suppression of tumor lymphangiogenesis and lymph node metastasis by blocking vascular endothelial growth factor receptor 3 signaling"J. Natl. Cancer Inst.. 94. 785-787 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Mizuno, K., et al.: "Aberrant hypermethylation of the CHFR prophase checkpoint gene in human lung cancers"Oncogene. 21. 2328-2333 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Osada, H., et al.: "Frequent and Histological type-specific inactivation of 14-3-3σin human lung cancers"Oncogene. 21. 2418-2424 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Koshikawa, K., et al.: "CLCP1,in a highly metastatic lung cancer subline as well as in lung cancers in vivo"Oncogene. 21. 2822-2828 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yatabe, Y., et al.: "TTF-1 expression in pulmonary adenocarcinomas"Am. J. Surg. Pathol.. 26. 767-773 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kozaki, K., et al.: "Multi-faceted analyses of a highly metastatic human lung cancer cell line NCI-H460-LNM35 suggest mimicry of inflammatory cells in metastasis"Oncogene. 20. 4228-4234 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Haruki, N., et al.: "Persistent increase in chromosome instability in lung cancer : possible indirect involvement of p53 inactivation"Am. J. Cancer Res.. 159. 1345-1352 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Masuda, A., et al.: "Protective function of p27^<KIP1> against apoptosis in small cell lung cancer cells in unfavorable microenvironments"Am. J. Pathol.. 158. 87-96 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Konishi, H., et al.: "Identification of frequent G2 checkpoint impairment and a homozygous deletion of 14-3-3ε at 17p13.3 in small cell lung cancers"Cancer Research.. 62. 271-276 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yoshida, K., et al.: "Association between the dopamine D2 receptor A2/A2 genotype and smoking behavior in the Japanese"Cancer Epidemiol., Biomark., & Prev.. 10. 403-405 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Osada, H., et al.: "Heterogeneous TGF-β unresponsiveness and loss of TGFβRII expression caused by histone deacetylation in lung cancer cell lines"Cancer Res.. 61. 8331-8339 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kozaki,K. et al.: "In vivo selected human lung cancer cell line H460-LNM35 consistently exhibits lymphogenous metastasis via both subcutaneous and orthotopic propagation."Cancer Res.. 69. 2535-2540 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yanagisawa,K. et al.: "Heterogeneities in the biological and biochemical functions of Smad2 and Smad4 mutants naturally occurring in human lung cancers."Oncogene. 19. 2305-2311 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yatabe,Y. et al.: "Topographical distributions of allelic loss in individual non-small cell lung cancers."Am.J.Pathol.. 157. 985-993 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hida,T. et al.: "Cyclooxygenase (COX)-2 inhibitor induces apoptosis and enhances cytotoxicity of various anticancer agents in non-small cell lung cancer cell lines."Clin.Cancer Res.. 6. 2006-2011 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Haruki,N. et al: "Histological type-selective, tumor-predominant expression of a novel CHK1 isoform and infrequent in vivo somatic CHK2 mutation in small cell lung cancer."Cancer Res.. 60. 4689-4692 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Masuda,A. et al.: "Protective function of p27^<KIP1> against apoptosis in small cell lung cancer cells in unfavorable microenvironments."Am.J.Pathol.. 158. 87-96 (2001)

    • Related Report
      2000 Annual Research Report

URL: 

Published: 2000-04-01   Modified: 2018-03-28  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi