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ID 30009
フルテキストURL
著者
Hanafusa, Tadashi Okayama University Advanced Science Research Center, Department of Radiation Research, Shikata Laboratory
Shinji, Toshiyuki Department of Laboratory Medicine, Okayama University Graduate School of Medicine and Dentistry
Shiraha, Hidenori First Department of Internal Medicine, Okayama University Graduate School of Medicine and Dentistry
Nouso, Kazuhiro First Department of Internal Medicine, Okayama University Graduate School of Medicine and Dentistry
Iwasaki, Yoshiaki First Department of Internal Medicine, Okayama University Graduate School of Medicine and Dentistry
Yumoto, Eichiro First Department of Internal Medicine, Okayama University Graduate School of Medicine and Dentistry
Ono, Toshiro Okayama University Advanced Science Research Center, Department of Radiation Research, Shikata Laboratory
Koide, Norio Department of Laboratory Medicine, Okayama University Graduate School of Medicine and Dentistry
抄録

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.

備考
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.
発行日
2005-01-20
出版物タイトル
BMC Cancer
5巻
出版者
BioMed Central
ISSN
1471-2407
NCID
AA12034763
資料タイプ
学術雑誌論文
言語
English
OAI-PMH Set
岡山大学
著作権者
Hanafusa et al; licensee BioMed Central Ltd.
論文のバージョン
publisher
査読
有り
DOI
PubMed ID
Web of Sience KeyUT
Submission Path
surgery/2