| Project/Area Number |
09671140
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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 |
Hematology
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| Research Institution | Hyogo College of Medicine |
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Principal Investigator |
TAMURA Shu Hyogo College of Medicine, Second Department of Internal Medicine, Assistant professor, 医学部, 助手 (30236749)
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| Co-Investigator(Kenkyū-buntansha) |
HASHIMOTO Tomoko (TAMAOKI) Hyogo College of Medicine, Department of Genetics, Associate professor, 医学部, 助教授 (10172868)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1998: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1997: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | ATBF1 / Acute myeloid leukemia / retinoic acid / gene therapy |
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| Research Abstract |
ATBF1-A is a transcription factor of 404 kDa in size contains four homeodomains and 23 zinc fingers. We previously reported that the level of ATBF1 -A transcripts is elevated when P19 embryonal carcinoma cells are induced to differentiate into neuronal cells by treatment with retinoic acid (RA). To further analyze the relationship between the expression of ATBF1-A and neuronal differentiation, we used in this study F9 embryonal carcinoma cells incapable of neuronal differentiation and RAC65 cells which differentiate into neuronal cells by 9-cis RA or 13-cis RA.Western blotting using polyclonal antibody which react with the first homeodomain of ATBF1 demonstrate that a 404kD protein is a nuclear protein and become detectable in P19 cells after three hours following treatment of all-trans RA (ATRA). 9-cis RA and 13-cis RA also induced ATBF1-A expression as well as neuronal differentiation in P19 cells. In RAC65 cells, expression of ATBF1-A was induced by 9- and 13-cis RA and, to a much lesser degree, by ATRA.In F9 cells no ATBF1 -A expression was induced by treatment with ATRA.Treatment with okadaic acid (OA), which is a potent inhibitor of protein phosphatase 2A, suppress neuronal differentiation of P19 cells as well as expression of ATBF1-A, indicating that an ATBF1-A functions as a single polypeptide and its expression is closely correlated with neuronal differentiation in response to retinoids. To elucidate whether the increment of ATBF1 -A expression is due to the elevation of ATBF1-A promoter activity, dual luciferase assay was performed. After 2 days of ATRA treatment, approximately 10-fold elevation of ATBF1-A promoter activity was seen in P19 cells. For gene therapy of refractory acute myeloid leukemia cells, we are now introducing ATBF1-A promoter region into various leukemia cells to induce to differentiate mature myelocytes by the treatment with ATRA.
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