| Project/Area Number |
23590997
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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 |
Gastroenterology
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| Research Institution | Aichi Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
KONISHI Hiroyuki 愛知医科大学, 医学部, 教授 (20344335)
NAKADE Yukiomi 愛知医科大学, 医学部, 講師 (70431400)
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| Project Period (FY) |
2011 – 2013
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 肝癌 / 細胞周期 / p53 / delta-N40p53 / p21 / G1/S / TP53 / 遺伝子ターゲッティング / △N40p53 / knock-out / 内在性遺伝子破壊 / 肝細胞 / AAV |
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| Research Abstract |
Using gene targeting with AAV vectors, we established hetero knock-out HepG2 cells clones (p53+/-) of which Exon2 in endogeneous TP53 alleles were destroyed. However, TP53 homo knock-out HepG2 cells clones have not been obtained. These results derived a hypothesis that p53 might be essential for cell proliferation in HepG2 cells, but knock down of expression of p53 using siRNA did not decrease cell proliferation.
On the other hand, we found that p53+/- cells constantly expressed deltaN40p53, an isoform of p53. Since the function of deltaN40p53 has been known little in liver cancer, we investigated the function of deltaN40p53 in HepG2 cells by using several methods. Our studies revealed that deltaN40p53 enhanced the expression of p21 and induced an increase of G1/S arrest, that is, deltaN40p53 made up for the function of p53 and suppressed tumor cell proliferation and induced cellular senescence in HepG2 cells when the expression of p53 was reduced.
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