2004 Fiscal Year Final Research Report Summary
Multifaceted analysis of molecular pathogenesis of human lung cancers
| Project/Area Number |
12213163
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Nagoya University (2004)
Aichi Cancer Center Research Institute (2000-2003) |
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Principal Investigator |
TAKAHASHI Takashi Nagoya University, Div. of Mol. Carcinog., Professor, 大学院医学系研究科, 教授 (50231395)
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| 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)
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| Project Period (FY) |
2000 – 2004
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| Keywords | molecular oncology / lung cancer / expression profiling / microarray / bioinformatics / metastasis / checkpoint |
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| 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.
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[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.
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Journal Title
Oncogene 23
Pages: 5360-5370
Description
「研究成果報告書概要(欧文)」より
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[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.
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Journal Title
Cancer Res. 64
Pages: 3753-3760
Description
「研究成果報告書概要(欧文)」より
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[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.
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Journal Title
Am.J.Pathol. 159
Pages: 1345-1352
Description
「研究成果報告書概要(欧文)」より
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