| Project/Area Number |
24590214
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Medical pharmacy
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| Research Institution | Tokai University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
KOMIYAMA Tomoyoshi 東海大学, 医学部, 准教授 (60439685)
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| Research Collaborator |
YU Shyr Vanderbilt大学, 癌センター, 教授
HANDE Kenneth R. Vanderbilt大学, 癌センター, 教授
BOKU Shikei 東海大学, 大学院医学研究科
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | がん / 薬剤反応性 / 薬物耐性 / 国際情報交換 米国 |
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| Outline of Final Research Achievements |
We investigated the mechanism of resistance using the human acute leukemia cell line MOLT3 and its idarubicin-resistant MOLT3/IDR by mtDNA and nuclear DNA analyses. We found altered candidate regions among the two cell lines. The ND3 mutation site (p.Thr61Ile) of mtDNA sequence was a unique mutation in the MOLT3/IDR. Moreover, we found five candidate genes by using array CGH analysis. Then, we focused on the GALNT2 gene among the five candidate genes. We sequenced the exon of GALNT2 gene and found a G1788K mutation of the stop codon position in MOLT3/IDR not in MOLT3. Because of this, the mutation led to 18 amino acids being added to the sequence in the GALNT2 gene. In addition, we confirmed the gene expression of this mutation region by RT-PCR. Furthermore, we predicted the protein structure of the mutated GALANT2 gene, and confirmed the conformational change of the ligand pocket. From our results, we speculated that these mutation genes might be related to idarubicin resistance.
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