1996 Fiscal Year Final Research Report Summary
Reglation of expression of human TCDD receptor and its physiological function.
| Project/Area Number |
07672408
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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 |
Biological pharmacy
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| Research Institution | Saitama Cancer Center |
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Principal Investigator |
HAYASHI Shin-ich Researchi lnstitute Saitama Cancer Center senior researcher, 研究所生化学部, 主任研究員 (60144862)
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| Project Period (FY) |
1995 – 1996
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| Keywords | TCDD receptor / Ah receptor / Estrogen receptor / human / transcriptional regulation / macrophage / transcription factor / nuclear receptor |
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| Research Abstract |
We investigated that the expression levels of Ah receptor varied among individuals and that an association with the expression of Amt and CYP1A1 was observed in peripheral blood. Since we found a high expression of human Ah receptor (AhR) mRNA in peripheral blood cells of individuals, the expression of this gene in blood cells was investigated in fractions of ucleated cells, revealing predominant expression of the Ah receptor gene in the monocyte fraction. Then the expression levels of AhR mRNA in various hematopoietic cell lines were examined together with those of Arnt and P450IA1. AhR was expressed at high levels in monocytoid cells, and at moderate levels in promyelocytic cells and erythroblastic cells. However, it was not detected in lymphoid cells, nor in erythroblasts. Furthermore, a specific induction of AhR during monocytic differetiation was observed. Our results suggest that AhR may play an important role in the function of monocytes and also in the eventual activation of environmental carcinogens. We then further investigated about the mechanisms of transcriptional regulation of AhR in monocytic cells ; i. e. , promoter analysis was performed using deletion mutants of 5'-flanking region of AhR gene fused with CAT-reportor plasmid. The transient transcription experiments of these plasmids showed significant transcription activity in monocytic cells and suggesting the existence of several positive or negative cis-elements in upstream region of AhR gene.
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