Development of gene therapy on lung cancer with regulation of expression and metabolism of cell cycle regulator p27Kip1
| Project/Area Number |
13557054
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Yokohama City University |
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Principal Investigator |
MATSUSE Takeshi Yokohama City University, medical center, professor, 医学部附属病院, 教授 (90199795)
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| Co-Investigator(Kenkyū-buntansha) |
MASUDA Miciaki Dokkyo university, school of medicine, professor, 医学部, 教授 (80199702)
GOSHIMA Yoshio Yokohama City University, school of medicine, professor, 医学部, 教授 (00153750)
KITAMURA Hitoshi Yokohama City University, school of medicine, professor, 医学部, 教授 (20094302)
TERAMOTO Shinji Tokyo university, school of medicine, lecturer, 医学部, 講師 (50282629)
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| Project Period (FY) |
2001 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥9,700,000 (Direct Cost: ¥9,700,000)
Fiscal Year 2003: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2002: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2001: ¥5,200,000 (Direct Cost: ¥5,200,000)
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| Keywords | cell cycle regulator / gene therapy / lung cancer / p27Kip 1 |
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| Research Abstract |
1.Regulation of apoptosis and necrosis of lung cancer cells by controlling the expression level of p27Kip1.
We investigated the role of p27Kip1 on cell viability in A549 lung adenocarcinoma cells. p27Kip1 overexpression with adenovirus vector reduced viral-induced apoptosis, and depletion of p27Kip1 with siRNA induced apoptosis. It was also speculated that cytoplasmic portion of p27Kip1 has this protective capacity against apoptosis.
2.The mechanism to regulate the intracellular localization of p27Kip1
Next, we checked the mechanism to regulate the intracellular localization of p27Kip1. Forced expression of p27Kip1 cDNA with substitution of S10, T157, and T198 to glutamate (phospho-mimetic) induced its cytoplasmic localization.
3.The role of p27Kip1 on cell cycle regulation in lung cancer cells.
We regulated p27Kip1 exptession level upward with adenovector and downward with the siRNA method in A549 cells. Although overexpression of p27Kip1 reduced cell cycle progression, its removal did not change cell cycle status.
4.The role of p27Kip1 on viability under the state of nutritional deficiency in lung cancer cells
We investigated the role of p27Kip1 on viability under the state of nutritional deficiency (amino acid or glucose) in A549 lung adenocarcinoma cells. It was supposed that amino acid or glucose deprivation induced cell cycle arrest and cell death, part of which is thought to be rescued by the existence of cytoplasmic p27Kip1.
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Report
(4 results)
Research Products
(5 results)
