2003 Fiscal Year Final Research Report Summary
Investigation of the mechanism of Fas-independent apoptosis in human neuroblastomas
| Project/Area Number |
14571708
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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 |
Pediatric surgery
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| Research Institution | St.Marianna University School of Medicine |
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Principal Investigator |
KOIZUMI Hirotaka KOIZUMI,Hirotaka, 医学部, 助教授 (10215155)
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| Co-Investigator(Kenkyū-buntansha) |
NAKADA Koonosuke St.Marianna University School of Medicine, Pediatric Surgery, Professor, 医学部, 教授 (70081734)
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| Project Period (FY) |
2002 – 2003
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| Keywords | neuroblastoma / apoptosis / Fas / caspase-3 / lamin A / PARP / H-Ras / autophagic degeneration |
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| Research Abstract |
We investigated the mechanism f Fas-independent apoptosis in neuroblastomas by examining expression profiles of caspase-3, lamin A, PARP [poly(ADP-ribose)polymerase] and H-Ras in 42 primary tissues. Immunohistochemically, most tumors expressed proforms of caspase-3, lamin A and PARP, but their active forms were exclusively localized in apoptotic cells. Favorable neuroblastomas tended to strongly express active caspase-3, lamin A and PARP. Whereas favorable tumors also overxpressed H-Ras, its localization appeared not to overlap the areas where tumor cell death (i.e., apoptosis, necrosis or autophagic degeneration) occurred. These results indicate that a caspase-dependent pathway plays an important role in the occurrence of apoptosis in neuroblastoma, albeit recent studies have suggested an involvement of H-ras-mediated, caspase-independent mechanism in tumor regression. We also performed X-linked clonality analysis in fibrous dysplasia and nodular fasciitis and plan to employ this powerful technique to specify cell population(s) that is faceable to undergo apoptosis in neuroblastoma.
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