| Project/Area Number |
11670192
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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 |
Human pathology
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| Research Institution | Keio University |
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Principal Investigator |
UMEZAWA Akihiro Keio University, School of Medicine, Associate professor, 医学部, 助教授 (70213486)
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| Co-Investigator(Kenkyū-buntansha) |
FUKUMA Mariko Keio University, School of Medicine Instructor, 医学部, 助手 (60101995)
HATA Jun-ichi Keio University, School of Medicine Professor, 医学部, 教授 (90051614)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2000: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1999: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | apoptosis / EAT / mcl-1 / islet cell / transgenic mice / differentiation / immediate early gene |
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| Research Abstract |
Early human embryogenesis is chronicled by a well-regulated sequence of cell differentiation events and is likewise correlated with regulated removal of unnecessary cells by apoptosis. A model of early human embryonic development has been established by the use of embryonal carcinoma (EC) cell lines. NCR-G3 cells were established from a human testicular mixed EC and are able to differentiate into neuronal, myogenic, epithelial as well as the trophectodermal lineage.
The mitochondria is an important organelle regulating the early stages of the apoptotic pathway. Bcl-2 related proteins have been shown to localize mainly in the outer mitochondrial membrane and to modulate mitochondrial permeability. These important functions are believed to initiate the apoptotic mechanism. EAT/mcl-1 (EAT), which encodes a bcl-2 related protein, was originally isolated as a gene whose expression is induced at an early stage of differentiation in NCR-G3 cells. It has since been found to inhibit apoptosis un
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der a variety of apoptosis-inducing conditions. The human EAT gene was found to be identical in sequence with mcl-1, a member of the bcl-2 family, which was isolated from a human myeloid leukemia cell line during TPA-induced differentiation into the monocyte/macroahage lineage. The murine orthologue of the EAT gene has also been isolated and has been established to be similarly induced by RA in murine embryonic stem (ES) cells and murine EC cell lines such as TT2, PCC3 and F9. Therefore, EAT functions to enhance cell survival.
EAT is also known to be an immediate early gene that has an immediate response box in its 3' untranslated region like other immediate early genes such as c-fos, c-jun and colony stimulation factor-1. This evidence implicates a role for EAT in the cellular differentiation associated with embryogenesis. However, the precise expression pattern and intracellular localization during EC differentiation have not been elucidated. We developed the monoclonal antibody which reacts specifically to EAT and determined the localization of EAT in a human EC cell line. Furthermore, we determined the expression of bcl-2 related proteins in EC cells undergoing differentiation or apoptosis and human embryogenesis. Less
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