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ID 32948
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Author
Asaumi, Jun-ichi
Maki, Yuu
Nagai, Noriyuki
Kawasaki, Shoji
Tanaka, Noriaki
Matsubara, Nagahide
Kishi, Kanji
Abstract

Maspin, which belongs to the serine protease inhibitor (serpin) superfamily, has been proposed as a potent tumor suppressor that inhibits cell motility, invasion, angiogenesis, and metastasis. In the present study, we examined the effects of 5-aza-2'-deoxycytidine (5-aza-dC), a demethylating agent, and FR901228, a histone deacetylase (HDAC) inhibitor, on maspin expression in oral cancer cell tines. The expression levels of maspin mRNA were divided into two groups, which was the maspin tow-expressed and high-expressed cell lines in the 12 oral cancer cell lines. The maspin promoter contained only a few methylated CpG sites in the maspin low-expressed cell lines. Moreover, the methylation status was not altered after 5-aza-dC treatment. However, the transcription of the maspin gene was clearly increased following 5-aza-dC treatment in a number of oral cancer cell tines. These results imply that an action of 5-aza-dC is separate from induction of promoter demethylation. Treatment with FR901228 resulted in a time-dependent stimulation of the re-expression of maspin mRNA as early as 4 h after treatment in the maspin downregulated cells. The re-expression of the maspin gene may contribute to the recuperation of biological functions linked to FR901228 such as an inhibitory effect on tumor angiogenesis and cell invasion. These results indicate that maspin and its target genes may be excellent leads for future studies on the potential benefits of FR901228, a HDAC inhibitor, in cancer therapy.

Keywords
maspin
methylation
5-aza-2 '-deoxycytidine
FR901228
Note
Digital Object Identifer:10.1016/j.oraloncology.2003.12.008
Published with permission from the copyright holder. This is the institute's copy, as published in Oral Oncology, February 2004, Volume 40, Issue 6, Pages 597-603.
Publisher URL:http://dx.doi.org/10.1016/j.oraloncology.2003.12.008
Direct access to Thomson Web of Science record
Copyright © 2004 Elsevier Ltd. All rights reserved.
Published Date
2004-2
Publication Title
Oral Oncology
Volume
volume40
Issue
issue6
Start Page
597
End Page
603
Content Type
Journal Article
language
英語
Refereed
True
DOI
Web of Sience KeyUT
Submission Path
dentistry_general/9