Isolation of genomic instability genes that are associated with malignancy
Project/Area Number |
20590309
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Pathological medical chemistry
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Research Institution | Nagoya University |
Principal Investigator |
SUZUKI Motoshi Nagoya University, 大学院・医学系研究科, 講師 (80236017)
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Co-Investigator(Kenkyū-buntansha) |
MURATE Takashi 名古屋大学, 医学部, 教授 (30239537)
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Project Period (FY) |
2008 – 2010
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Project Status |
Completed (Fiscal Year 2010)
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Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2010: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
Keywords | DNA複製 / ゲノムインスタビリティー / 癌 / DNA修復 / 細胞周期 / 肺癌 / チェックポイント / マイクロアレー / ヒストン修飾 / チェックポインイ |
Research Abstract |
In examinations of 158 lung cancers and 5 mixtures of 10 normal lungs, cell cycle- and checkpoint-related genes generally showed mRNA expression increases in cancer, whereas POLD4 showed reduced mRNA in small cell lung cancer (SCLC). In the absence of POLD4, we observed defect in DNA repair activity, delay in cell cycle, and increased frequency of chromosomal break induction. Overexpression of an engineered POLD4 carrying silent mutations at the siRNA target site rescued these phenotypes, firmly establishing the role of POLD4 in these effects. In order to identify gene products that interact with POLD4, we performed an MS analysis using the immunoprecipitated protein fractions with POLD4, where ATM, CDC14 and other cell cycle checkpoint/progression proteins were detected. We further identified novel single nucleotide variations (SNV) in lung cancer cell lines. One of the SNV reduced the physical interaction ability with the catalytic subunit of pol delta. These results suggest that the newly identified SNV could be involved in the carcinogenesis by modifying DNA replication ability of DNA polymerase delta.
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Report
(4 results)
Research Products
(76 results)
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[Journal Article] Proteasomal Non-catalytic Subunit PSMD2 as a Potential Therapeutic Target in Association with Various Clinicopathologic Features in Lung Adenocarcinomas.2011
Author(s)
Matsuyama Y, Suzuki M, Arima C, Huang Q, Tomida S, Takeuchi T, Sugiyama R, Itoh Y, Yatabe Y, Goto H, Takahashi T.
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Journal Title
Related Report
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[Journal Article] Heterogeneous sphingosine-1-phosphate lyase gene expression and its regulatory mechanism in human lung cancer cell lines.2011
Author(s)
Ito H, Yoshida K, Murakami M, Hagiwara K, Sasaki N, Kobayashi M, Takagi A, Kojima T, Sobue S, Suzuki M, Tamiya-Koizumi K, Nakamura M, Banno Y, Nozawa Y, Murate T.
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Journal Title
Biochim Biophys Acta. 1811
Pages: 119-128
Related Report
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[Journal Article] Heterogeneous sphingosine-1-phosphate lyase gene expression and its regulatory mechanism in human lung cancer cell lines.2011
Author(s)
Ito H, Yoshida K, Murakami M, Hagiwara K, Sasaki N, Kobayashi M, Takagi A, Kojima T, Sobue S, Suzuki M, Tamiya-Koizumi K, Nakamura M, Banno Y, Nozawa Y, Murate T.
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Journal Title
Biochim Biophys Acta.
Volume: 1811
Pages: 119-128
Related Report
Peer Reviewed
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[Journal Article] Proteasomal Non-catalytic Subunit PSMD2 as a Potential Therapeutic Target in Association with Various Clinicopath ologic Features in Lung Adenocarcinomas.2011
Author(s)
Matsuyama Y, Suzuki M, Arima C, Huang Q, Tomida S, Takeuchi T, Sugiyama R, Itoh Y, Yatabe Y, Goto H, Takahashi T.
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Journal Title
Mol Carcinog.
Volume: 印刷中(未定)
Related Report
Peer Reviewed
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[Journal Article] Mechanism of increased PLD1 gene expression during early adipocyte differentiation process of mouse cell line 3T3-L1.2010
Author(s)
Gao S, Ito H, Murakami M, Yoshida K, Tagawa Y, Hagiwara K, Takagi A, Kojima T, Suzuki M, Banno Y, Ohguchi K, Nozawa Y, Murate T.
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Journal Title
J Cell Biochem. 109
Pages: 375-382
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[Journal Article] Regulation of DNA polymerase POLD4 influences genomic instability in lung cancer.2010
Author(s)
Huang QM, Tomida S, Masuda Y, Arima C, Cao K, Kasahara TA, Osada H, Yatabe Y, Akashi T, Kamiya K, Takahashi T, Suzuki M.
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Journal Title
Cancer Res. 70
Pages: 8407-8416
Related Report
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[Journal Article] ATRA inhibits ceramide kinase transcription in a human neuroblastoma cell line, SH-SY5Y cells : the role of COUP-TFI.2010
Author(s)
Murakami M, Ito H, Hagiwara K, Yoshida K, Sobue S, Ichihara M, Takagi A, Kojima T, Tanaka K, Tamiya-Koizumi K, Kyogashima M, Suzuki M, Banno Y, Nozawa Y, Murate T.
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Journal Title
J Neurochem. 112
Pages: 511-520
Related Report
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[Journal Article] Regulation of DNA polymerase POLD4 influences genomic instability in lung cancer.2010
Author(s)
Huang QM, Tomida S, Masuda Y, Arima C, Cao K, Kasahara TA, Osada H, Yatabe Y, Akashi T, Kamiya K, Takahashi T, Suzuki M.
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Journal Title
Cancer Res.
Volume: 70
Pages: 8407-8416
Related Report
Peer Reviewed
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[Journal Article] ATRA inhibits ceramide kinase transcription in a human neuroblastoma cell line, SH-SY5Y cells : the role of COUP-TFI.2010
Author(s)
Murakami M, Ito H, Hagiwara K, Yoshida K, Sobue S, Ichihara M, Takagi A, Kojima T, Tanaka K, Tamiya-Koizumi K, Kyogashima M, Suzuki M, Banno Y, Nozawa Y, Murate T.
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Journal Title
J Neurochem.
Volume: 112
Pages: 511-520
Related Report
Peer Reviewed
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[Journal Article] p27 deregulation by Skp2 overexpression induced by the JAK2V617 mutation.2009
Author(s)
Furuhata A, Kimura A, Shide K, Shimoda K, Murakami M, Ito H, Gao S, Yoshida K, Tagawa Y, Hagiwara K, Takagi A, Kojima T, Suzuki M, Abe A, Naoe T, Murate T.
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Journal Title
Biochem Biophys Res Commun. 383
Pages: 411-416
Related Report
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[Journal Article] GATA-1 and GATA-2 binding to 3' enhancer of WT1 gene is essential for its transcription in acute leukemia and solid tumor cell lines.2009
Author(s)
Furuhata A, Murakami M, Ito H, Gao S, Yoshida K, Sobue S, Kikuchi R, Iwasaki T, Takagi A, Kojima T, Suzuki M, Abe A, Naoe T, Murate T.
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Journal Title
Leukemia. 23
Pages: 1270-1277
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[Journal Article] Mutated Ras induced PLD1 gene expression in human colon cancer cell lines and a mouse cell line of NIH3T3.2009
Author(s)
Gao S, Murakami S, Ito S, Furuhata A, Yoshida K, Tagawa Y, Hagiwara K, Takagi A, Kojima T, Suzuki M, Banno Y, Nozawa K, Murate T.
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Journal Title
Nagoya J Med Sci. 71
Pages: 127-136
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[Journal Article] Transcriptional regulation of neutral sphingomyelinase 2 gene expression of a human breast cancer cell line, MCF-7, induced by the anti-cancer drug, daunorubicin.2009
Author(s)
Ito H, Murakami M, Furuhata A, Gao S, Yoshida K, Sobue S, Hagiwara K, Takagi A, Kojima T, Suzuki M, Banno Y, Tanaka K, Tamiya-Koizumi K, Kyogashima M, Nozawa Y, Murate T.
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Journal Title
Biochim Biophys Acta. 1789
Pages: 681-690
Related Report
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[Journal Article] PCNA mono-ubiquitination and activation of translesion DNA polymerases by DNA polymerase alpha.2009
Author(s)
Suzuki M, Niimi A, Limsirichaikul S, Tomida S, Huang Q, Izuta S, Usukura J, Itoh Y, Hishida T, Akashi T, Nakagawa Y, Kikuchi A, Pavlov Y, Murate T, Takahashi T.
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Journal Title
J Biochem. 146
Pages: 13-21
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[Journal Article] v-Src oncogene product increases sphingosine kinase 1 expression through mRNA stabilization : alteration of AU-rich element-binding proteins.2008
Author(s)
Sobue S, Murakami M, Banno Y, Ito H, Kimura A, Gao S, Furuhata A, Takagi A, Kojima T, Suzuki M, Nozawa Y, Murate T.
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Journal Title
Oncogene. 27
Pages: 6023-6033
Related Report
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[Journal Article] Implications of sphingosine kinase 1 expression level for the cellular sphingolipid rheostat : relevance as a marker for daunorubicin sensitivity of leukemia cells.2008
Author(s)
Sobue S, Nemoto S, Murakami M, Ito H, Kimura A, Gao S, Furuhata A, Takagi A, Kojima T, Nakamura M, Ito Y, Suzuki M, Banno Y, Nozawa Y, Murate T.
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Journal Title
Int J Hematol. 87
Pages: 266-275
Related Report
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[Journal Article] Implications of sphingosine kinase lexpression level for the cellular sphingolipid rheostat : relevance as a marker for daunorubicin sensitivity of leukemia cells2008
Author(s)
Sobue S, Nemoto S, Murakami M, Ito H, Kimura A, Gao S, Furuhata A, Takagi A, Kojima T, Nakamura M, Ito Y, Suzuki M, Banno Y, Nozawa Y, Murate T
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Journal Title
Int J Hematol 87
Pages: 266-275
Related Report
Peer Reviewed
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[Journal Article] v-Src oncogene product increases sphingosine kinase 1 expressi on through mRNA stabilization : alteration of AU-rich element-binding proteins2008
Author(s)
Sobue S, Murakami M, Banno Y, Ito H, Kimura A, Gao S, Furuhata A, Takagi A, Kojima T, Suzuki M, Nozawa Y, Murate T
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Journal Title
Oncogene 27
Pages: 6023-6033
Related Report
Peer Reviewed
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[Presentation] Epigenetic reduction of POLD4/p12 and genomic instability induction in small cell lung cancer.2010
Author(s)
Huang QM, Tomida S, Masuda S, Arima C, Kasahara T, Osada H, Akashi T, Murate T, Kamiya K, Takahashi T, Suzuki M
Organizer
International Conference on Radiation and Cancer Biology at Nagasaki 2010'
Place of Presentation
Nagasaki
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[Presentation] Epigenetic reduction of POLD4/p12 and genomic instability induction in small cell lung cancer.2009
Author(s)
Huang QM, Tomida S, Masuda S, Arima C, Kasahara T, Osada H, Akashi T, Murate T, Kamiya K, Takahashi T, Suzuki M
Organizer
The 3rd International Symposium on "Molecular Science of Fluctuations toward Biological Functions"
Place of Presentation
Nagoya
Related Report
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[Presentation] Epigenetic reduction of POLD4/p12 and genomic instability induction in small cell lung cancer.2009
Author(s)
Huang QM, Tomida S, Masuda S, Arima C, Kasahara T, Osada H, Akashi T, Murate T, Kamiya K, Takahashi T, Suzuki M
Organizer
The 2nd International Symposium of Nagoya Univ GCOE
Place of Presentation
Nagoya
Related Report
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[Presentation] Elucidation of Proteasomal Non-catalytic Subunit PSMD2 as Potential Therapeutic Target and Its Co-upregulation with Proteasome Pathway Genes in Association with Various Clinicopathologic Features in Lung Adenocarcinomas.2009
Author(s)
Matsuyama M, Suzuki M, Arima C, Huang QM, Tomida S, Takeuchi T, Sugiyama R, Itoh Y, Yatabe Y, Goto H, Takahashi T
Organizer
The 2nd International Symposium of Nagoya Univ GCOE
Place of Presentation
Nagoya
Related Report
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[Presentation] Epigenetic reduction of POLD4/p12 and genomic instability induction in small cell lung cancer.2009
Author(s)
Huang QM, Tomida S, Masuda S, Arima C, Kasahara T, Osada H, Akashi T, Murate T, Kamiya K, Takahashi T, Suzuki M
Organizer
The 19th International Symposium of Hiroshima Cancer Seminar in conjugation with Three Universities' Consortium
Place of Presentation
Hiroshima(Best Poster Award)
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