| Co-Investigator(Kenkyū-buntansha) |
YAMADA Takeo School of Medicine, Keio University, Instructor, 医学部, 助手 (60230463)
UMEZAWA Akihiro School of Medicine, Keio University, Associate Professor, 医学部, 講師 (70213486)
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| Research Abstract |
The aim of this study was to isolate the essential genes in retinoic acid (RA)-induced differentiation of human EC cells, NCR-G3 cell. We isolated a novel gene, EAT which transiently expressed in the early stage of differentiation and has homology with bcl-2, a cell death-preventing molecule. We obtained following results by analyzing this novel gene, EAT.
To elucidate expression of EAT in normal and fetal tissue, a murine monoclonal antibody, 3A2 was generated by use of recombinant protein to EAT. By immnohistochemical studies, EAT expression was observed in a wide variety of human fetal and adult tissues, including those of epithelial, hematopoietic and endocrine cells. In murine embryos, EAT was induced rapidly after fertilization reaching maximum level at the from the 2 - to 8-cell stage and then decrease to below unfertilized egg levels in blastocyst.
2) We determined whether the apoptotic cell death induced by chemotherapeutic agents could be inhibited by EAT as is reported with Bcl-2. Cells transfected with EAT showed higher resistance to CDDP or among other chemotherapeutic agents tested. DNA fragmentation of the parental cells following treatment with CDDP and carboplatin was observed in a concentration-dependent manner. In contrast, cells transfected with EAT did not show DNA fragmentation following treatment with the same concentration of these drugs. Acute tubular necrosis induced by CDDP administration did not occur in the EAT transgenic mice.
These results suggest that EAT may play an important role in early embryogenesis and sequential cell function by its anti-apoptotic functions.
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