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ID 30009
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Author
Shinji, Toshiyuki
Iwasaki, Yoshiaki ORCID Kakenhi
Yumoto, Eichiro
Koide, Norio
Abstract

Background: Insulin-like growth factor binding protein (IGFBP)-3 functions as a carrier of insulinlike growth factors (IGFs) in circulation and a mediator of the growth suppression signal in cells. There are two reported p53 regulatory regions in the IGFBP3 gene; one upstream of the promoter and one intronic. We previously reported a hot spot of promoter hypermethylation of IGFBP-3 in human hepatocellular carcinomas and derivative cell lines. As the hot spot locates at the putative upstream p53 consensus sequences, these p53 consensus sequences are really functional is a question to be answered.
Methods: In this study, we examined the p53 consensus sequences upstream of the IGFBP-3 promoter for the p53 induced expression of IGFBP-3. Deletion, mutagenesis, and methylation constructs of IGFBP-3 promoter were assessed in the human hepatoblastoma cell line HepG2 for promoter activity.
Results: Deletions and mutations of these sequences completely abolished the expression of IGFBP-3 in the presence of p53 overexpression. In vitro methylation of these p53 consensus sequences also suppressed IGFBP-3 expression. In contrast, the expression of IGFBP-3 was not affected in the absence of p53 overexpression. Further, we observed by electrophoresis mobility shift assay that p53 binding to the promoter region was diminished when methylated.
Conclusion: From these observations, we conclude that four out of eleven p53 consensus sequences upstream of the IGFBP-3 promoter are essential for the p53 induced expression of IGFBP-3, and hypermethylation of these sequences selectively suppresses p53 induced IGFBP-3 expression in HepG2 cells.

Note
Digital Object Identifer:10.1186/1471-2407-5-9
Published with permission from the copyright holder. This is the institute's copy, as published in BMC Cancer, 20 January 2005, 5:9.
Publisher URL:http://dx.doi.org/10.1186/1471-2407-5-9
© 2005 Hanafusa et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Published Date
2005-01-20
Publication Title
BMC Cancer
Volume
volume5
Publisher
BioMed Central
ISSN
1471-2407
NCID
AA12034763
Content Type
Journal Article
language
英語
Copyright Holders
Hanafusa et al; licensee BioMed Central Ltd.
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publisher
Refereed
True
DOI
PubMed ID
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Submission Path
surgery/2