2003 Fiscal Year Final Research Report Summary
Elucidation of new molecular mechanism of cancer caused by gene promoter methylation and its clinical aplication
| Project/Area Number |
14571198
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | OKAYAMA UNIVERSITY |
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Principal Investigator |
MATSUBARA Nagahide Okayama University, Medical and Dental Hospital, Assistant Professor, 医学部・歯学部附属病院, 助手 (70314672)
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| Co-Investigator(Kenkyū-buntansha) |
ISOZAKI Hiroshi Okayama University, Medical and Dental Hospital, Associate Professor, 医学部・歯学部附属病院, 助教授 (50151436)
TANAKA Noriaki Okayama University, Graduate School of Medicine and Dentistry, Professor, 大学院・医歯学総合研究科, 教授 (10127566)
SHIMIZU Kenji Okayama University, Graduate School of Medicine and Dentistry, Professor, 大学院・医歯学総合研究科, 教授 (10037286)
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| Project Period (FY) |
2002 – 2003
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| Keywords | gastroenterological cancer / carcinogenesis / genetic alteration / epigenetic alteration / colorectal cancer / gastric cancer / esophageal cancer / microsatellite instability |
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| Research Abstract |
We have been studied molecular mechanisms of gastrointestinal carcinogenesis and cancer progression. One of our research focuses is colorectal cancer, and we have found the cancer specific mutation in E2F4, one of the important transcription factors, as a new gene strongly related to the colorectal cancer progression characterized as microsatellite instability phenotype (published 2 articles in Cancer Res.). We also found ING-1 as a new important target gene in esophageal squamouse cell cancer (published in Cancer Res.). We also studied the molecular events occur in early stages (just invaded into submucosa) of colorectal cancer, and we found high prevalence of microsatellite in low frequency (MSI-L) in this group of cancers (published in Cancer Res. ). Frequency of MSI-L in advanced colorectal cancer is really low around 10%, however, we found MSI-L phenotype in 50% of the early stage colorectal cancers. Now more and more researchers are involved in the new MSI-L carcinogenesis pathwa
… More
y, which was thought to be an artifact an thus not a meaningful phenomenon.
Recently not only genetic, including mutations and deletions, but also epigenetic phenomenon are involved in many types of carcinogenesis. The most typical epigenetic alteration is the promoter hypermethylation, which causes the silencing of the gene. DNA methylation occurs preferentially within dense clusters of CpG sites know as CpG islands. Therefore reference is made to a CpG island methlator phenotype (CIMP). Most of our recent work was focused on this promoter methylation of multiple genes in gastrointestinal cancers, and we made tremendous progress in this field. We found that the important DNA repair gene MGMT (O6-methylguanine DNA methyltransferase) is controlled of its expression by promoter methylation, by analyzing precise map of methylation in its promoter. We also found that the level of methylation is strongly related to the prognosis and chemoresistance of colorectal cancers (Clinical Cancer Research). Furthermore, we classified colorectal cancer by mutational status of KRAS and BRAF, and showed close correlation to the methylation status of the multiple promoter methylation in colorectal cancer (Journal of Clinical Oncology). Less
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Research Products
(31 results)
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[Journal Article] Effects of histone deacetylase inhibitor FR901228 on expression level of telomerase reverse transcriptase in oral cancer.2004
Author(s)
Jun Murakami, Junichi Asaumi, Noriko Kawai, Hidetsugu Tsujigiwa, Yoshinobu Yanagi, Hitoshi Nagatsuka, Tetsuyoshi Inoue, Susumu Kokeguchi, Shoji Kawasaki, Masahiro Kuroda, Noriaki Tanaka, Nagahide Matsubara, Kanji Kishi
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Journal Title
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Colorectal cancer with mutation in BRAF, KRAS, and wild-type with respect to both oncogenes show different patterns of DNA methylation.2004
Author(s)
Takeshi Nagasaka, Hiromi Sasamoto, Kenji Notohara, Harry M.Cullings, Masanori Takeda, Keigo Kimura, Takeshi Kambara, Donald G.MacPhee, Joanne Young, Barbara A.Leggett, Jeremy R.Jass, Noriaki Tanaka, Nagahide Matsubara
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Journal Title
J. Clip. Oncol. 22(22)
Pages: 4584-4594
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] BRAF mutation is associated with DNA methylation in serrated polyps and cancers of the colorectum.2004
Author(s)
Takeshi Kambara, Lisa A.Simms, Vicki L.J.Whitehall, Kevin J.Spring, Coral V.A.Wynter, Michael D.Walsh, Melissa A.Barker, Sven Arnold, Andrina McGivern, Nagahide Matsubara, Noriaki Tanaka, Tetsuro Higuclu, Joanne Young, Jeremy R.Jass, Barbara A.Leggett
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Journal Title
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Influence of CpG island methylation status in 06-methylguanine-DNA methyltransferase expression of oral cancer cell lines.2004
Author(s)
Murakami, J., Asaumi, J., Maki, Y., Tsujigiwa, H., Nagatsuka, H., Kokeguchi, S., Inoue, T., Kawasaki, S., Tanaka, N., MacPhee, D., Matsubara, N., Kishi, K.
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Journal Title
Oncol. Rep. 12
Pages: 339-45
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Effects of demethylating agent 5-aza-2'-deoxycytidine and histone deacetylase inhibitor FR901228 on maspin gene expression in oral cancer cell lines.2004
Author(s)
Murakami, J., Asaumi, J., Maki, Y., Tsujigiwa, H., Kuroda M., Nagai, N., Yanagi, Y., Inoue, T., Kawasaki, S., Tanaka, N., Matsubara.N., Kishi K.
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Journal Title
Oral Oncol. 40
Pages: 597-603
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Role of Inherited Defects of MYH in the Development of Sporadic Colorectal Cancer.2004
Author(s)
Takeshi Kambara, Vicki L.J.Whitehall, Kevin J.Spring, Melissa A.Barker, Sven Arnold, Coral V.A.Wynter, Nagahide Matsubara, Noriaki Tanaka, Joanne P.Young, Barbara A.Leggett, Jeremy R.Jass
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Journal Title
Gene Chromosome Canc. 40
Pages: 1-9
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Allelic loss of a common microsatellite marker MYcL1: a useful prognostic factor of poor outcomes in colorectal cancer.2004
Author(s)
Kambara, T., Sharp, GB., Nagasaka, T., Takeda, M., Sasamoto, H., Nakagawa, H., Isozaki, H., MacPhee, D.G., Jass, J.R., Tanaka, N., Matsubara, N.
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Journal Title
Clinical Cancer Res. 10
Pages: 1758-1763
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Hypermethylation of 06-methylguanine-DNA methyltransferase promoter may predict nonrecurrence after chemotherapy in colorectal cancer cases.2003
Author(s)
Nagasaka, T., Sharp, GB., Notohara, K., Kambara, T., Sasamoto, H., Isozaki, H., MacPhee, D.G., Jass, J.R., Tanaka, N., Matsubara, N.
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Journal Title
Clinical Cancer Res. 9
Pages: 5306-5312
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Low-level microsatellite instability in most colorectal carcinomas. Cancer Res., 62: 1166-1170, 2002.2002
Author(s)
Jass, J.R., Whitehall, V.L.J., Young, J., Leggett, B., Meltzer, S.J., Matsubara.N., Fishel, R.: Correspondence re: P.Laiho, et al.
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Journal Title
Cancer Res. 62
Pages: 5988-5990
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Instabilotyping reveals unique mutational spectra in microsatellite-unstable gastric cancers.2002
Author(s)
Mori, Y., Sato, F., Selaru, F.M., Olaru, A., Perry, K., Kimos, M.C., Tamura, G., Matsubara, N., Wang, S., Xu, Y., Yin, J., Zou, T.T., Leggett, B., Young, J., Nukiwa, T., Stine, O.C., Abraham, J.M., Shibata, D., Meltzer, S.J.
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Journal Title
Cancer Res. 62
Pages: 3641-3645
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Allelic imbalance and microsatellite instability in plasma DNA released from polyclonal pancreatic adenocarcinoma.2002
Author(s)
Moriyama, H., Matsubara, N., Kambara, T., Mori, M., Matsuoka, J., Yoshino, T., Takakura, N., Shimizu, K., Tanaka, N.
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Journal Title
Int. J. Oncol. 21
Pages: 949-956
Description
「研究成果報告書概要(欧文)」より
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