1998 Fiscal Year Final Research Report Summary
Identification of alpha-fetoprotein silencer and analysis of its regulatory mechanisms
| Project/Area Number |
09670558
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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 |
Gastroenterology
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| Research Institution | Nagasaki University |
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Principal Investigator |
NAKATA Keisuke Nagasaki University, School of Medicine, Assistant Professor, 医学部, 助教授 (40217740)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAO Kazuhiko Nagasaki University, Health Research Center, Lecturer, 保健管理センター, 講師 (00264218)
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| Project Period (FY) |
1997 – 1998
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| Keywords | alpha-Fetoprotein / Albumin / Silencer / HMGI-C / Rb gene / Ras gene |
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| Research Abstract |
The a-fetoprotein (AEP) silencer activity is relevant to repression of AFP expression after birth. Moreover, down-regulation of the silencer activity would lead to re-expression of the AFP gene in the hepatocarcinogenetic process. In the present study, the AFP silecer interacted with its enhancer, resulting in the inhibition of the enhancer activity. Furthermore, repression of the AFP enhancer activity depressed both the AFP and albumin gene expression. When retinoblastoma (Rb) gene or ras gene were transduced in HuH-7 human hepatoma cells, transduction of Rb gene up-regulated expression of the hepatocyte nuclear factor-1 (HNF-1) gene, a liver-specific transcriptional factor, which stimulated both the AFP and albumin gene transcription through activation of their promoters. Transduction of ras gene induced the suppression of the AFP enhancer activity and repressed the AFP gene transcription. In addition, the Rb gene transduction in HuH-7 cells not only stimulated HNF-1 expression but also promoted contact inhibition of cell growth. Thus the Rb gene was considered to function as a differeatiation inducer, although it did not directly induce the AFP silencer activity.
HMGI-C is a key factor involved in DNA loop formation and expressed highly in fetal organs or certain malignant cells. Expression of HMGI-C was analyzed in human hepatoma cell lines by means of RT-PCR.Its expression was apparenty higher in AFP-producing cells than nonproclucing cells. This would suggest the association of HMGI-C expression with the AFP silencer activity in human hepatoma cells.
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Research Products
(14 results)
