2000 Fiscal Year Final Research Report Summary
Anti-apoptotic function of EAT/mcl-1 on diseases
| 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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| 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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Research Products
(7 results)
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[Publications] Sano, M., Umezawa, A., Abe, H., Akatsuka, A., Nonaka, S., Shimizu, H., Fukuma, M., Hata, J-i.: "EAT/mcl-1 expression in the human embryonal carcinoma cells undergoing differetiation and apoptosis."Exp Cell Res. (in press).
Description
「研究成果報告書概要(欧文)」より
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[Publications] Fukuchi, Y., Kizaki, M., Yamato, K., Kawamura, C., Umezawa, A., Hata, J-i., Nishihara, T.and Ikeda, Y.: "Mcl-1, an early-induction molecule, modulates activin A-induced apoptosis and differentiation of CML cells."Oncogene. (in press).
Description
「研究成果報告書概要(欧文)」より
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[Publications] Sano, M., Umezawa, A., Suzuki, A., Shimoda, K., Fukuma, M., and Hata, J-i: "Involvement of EAT/mcl-1, an anti-apoptotic bcl-2 related gene, in murine embryogenesis and human development."Exp.Cell Res.. 259(1). 127-139 (2000)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Wakabayashi, K., Saito, H., Ebinuma, H., Saito, Y., Takagi, T., Nakamura, M., Umezawa, A., Hata, J., and Ishii, H.: "Bcl-2 related proteins are dramatically induced at the early stage of differentiation in human liver cancer cells by a histone deacetylase inhibitor projecting an antiapoptotic role during this period."Oncol Rep.. 7(2). 285-288 (2000)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Suzuki, A., Umezawa, A., Sano, M., Nozawa, S., and Hata, J-i: "Involvement of EAT/mcl-1, a bcl-2 related gene, in the apoptotic mechanisms undering human placental development and maintenance."Placenta.. 21(2). 177-183 (2000)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Okita, H., Umezawa, A., Fukuma, F., Ando, T., Urano, F., Sano, M., Nakata, Y., Mori, T., and Hata, J-i: "Acute myeloid leukemia possessing jumping translocation is related to highly elevated levels of EAT/mcl-1, a Bcl-2 related gene with anti-apoptotic functions."Leukemia Res.. 24(1). 73-77 (2000)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Matsushita, K., Umezawa, A., Iwanaga, S., Oda, T., Okita, H., Kimura, K., Shimada, M., Tanaka, M., Sano, M., Ogawa, M., and Hata, J-i: "The EAT/mcl-1 gene, an inhibitor of apoptosis, is up-regulated in the early stage of acute myocardial infarction."Biochim Biophys Acta.. 1472(3). 471-478 (1999)
Description
「研究成果報告書概要(欧文)」より
