2001 Fiscal Year Final Research Report Summary
Analysis of the mechanism for suppression of childhood leukemia via ARF-p53 pathway
| Project/Area Number |
12670736
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Shinshu University School of Medicine |
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Principal Investigator |
KAMIJO Takehiko Shinshu University, School of Medicine, Associate Professor, 医学部・附属病院小児科, 講師 (90262708)
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| Co-Investigator(Kenkyū-buntansha) |
KOIKE Kenichi Shinshu University, School of Medicine , Associate Professor, 医学部・小児科, 助教授 (40143979)
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| Project Period (FY) |
2000 – 2001
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| Keywords | ARF / p53 / tumor suppressor / leukemia / apoptosis |
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| Research Abstract |
ARF, a tumor suppressor gene product, is seemed to protect cells from leukemic transformation via p53-dependent pathway. In this study, we performed the analysis of lymphocyte surface markers on ARF-null lymphocytes and examined hematopoietic cell colony formation from bone marrow cells cultured in the presence of several combinations of the cytokines. However, ARF-null cells did not possess specific surface makers and growth advantage compared to wild-type cells. ARF sensitizes cells to apoptosis in the presence of appropriate collateral signals. Therefore, we analyzed the mechanism of ARF-dependent apoptosis to study the role of ARF on tumor suppression. We demonstrated that ARF induces mitochondria-dependent apoptosis in p53 wild-type cells. We also found that ARF evokes cytochrome c release from mitochondria, decreases mitochondrial membrane potential and activates pro-caspase-9 to induce apoptosis. This pro-apoptotic cellular modulation appeared to be brought about by upregulation of the ratio of two sets of pro-apoptotic/anti-apoptotic initochondrial proteins, Bax/Bcl-2 and Bim/Bcl-2. Whereas downregulation of Bcl-2 by ARF was via a p53-dependent pathway, Bax and Bim upregulation was induced by serum starvation.
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Research Products
(10 results)
