2016 Fiscal Year Research-status Report
神経芽細胞腫予後良好因子の病態制御機構の解明と自然消退への応用
| Project/Area Number |
15K10921
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| Research Institution | Hiroshima University |
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Principal Investigator |
山岡 絵美 (福田絵美) 広島大学, 自然科学研究支援開発センター, 研究員 (20403503)
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| Co-Investigator(Kenkyū-buntansha) |
栗原 將 広島大学, 病院(医), 医科診療医 (40724894)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Keywords | 神経芽腫 / 予後因子 |
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| Outline of Annual Research Achievements |
Neuroblastoma(NB) is the most common solid tumor in infants and big cause of cancer death. NB arising from neural crest, is classified unfavorable and favorable outcome.
Recently, we compared gene expressions between favorable and unfavorable group by oligo-microarray and top hits genes were <I>DHRS3</I>, <I>NR0B1</I>, and <I>CYP26A1</I> in the favorable groups. We established overexpressing and silencing clones of five neuroblastoma cells using plasmid transfection or Retrovirus Tet-On expression system.
Of those overexpressing clones, especially SKNSH and NH12 expressing <I>DHRS3</I> represented reduced cell growth rate, inducing a G1 cell-cycle arrest, reduced colony formation ability, differentiated character within 10 days and mostly inducind cell death. We also found the ectopic expression of <I>DHRS3</I> promotes lipid droplet accumulation and that lead to cellular differentiation after TP53 activation.
Further RNA-seq analysis revealed that <I>DHRS3</I> and <I>NR0B1</I> expressing clones promotes cellular senescence and differentiation, whereas <I>CYP26A1</I> was not effective for the cellular malignancy.
So we suppose that <I>DHRS3</I> and <I>NR0B1</I> are the potential target for the treatment of neuroblastoma.
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| Current Status of Research Progress |
Current Status of Research Progress
3: Progress in research has been slightly delayed.
Reason
Tet-On遺伝子発現の結果、CYP26A1は予後良好因子として関与していない可能性がでてきたので、予後良好因子の候補から外し、ノックダウンモデル動物の作成は行わないことにした。
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| Strategy for Future Research Activity |
RNA-seqの遺伝子発現結果と照らし合わせながら、相関する候補遺伝子を絞り込み検討をすすめてゆく予定である。
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| Causes of Carryover |
消耗品を購入する予定で予算を残していたのですが、実験計画が遅れて購入できなかったので次年度に繰り越します。
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| Expenditure Plan for Carryover Budget |
次年度に消耗品として試薬を購入するために使用します。
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