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Research Paper
Regulation of RAR?1 Expression in Head and Neck Cancer Cells by Cell Density-Dependent Chromatin Remodeling
Emile M. Youssef, Jean-Pierre J. Issa and Reuben Lotan
volume 3 | issue 10
october 2004Pages: 1002-1006
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Retinoids have shown siginificant activities in cancer prevention and therapy. Many of their effects are mediated by nuclear retinoid receptors including retinoic acid receptors (RARs ?, ?, and ?) and retinoid X receptors (RXRs ?, ?, and ?. Human retinoic acid receptor ? (RAR?) has three different isoforms: ?1, ?2, and ?4. The tumor suppressive characteristics of RAR?2, its silencing by promoter hypermethylation, and its re-expression following demethylation have been reported. In contrast, RAR?1, an embryonic isoform with restricted expression in adult tissues has been linked to carcinogenesis. However, factors regulating RAR?1 expression have not yet been clarified. During studies on the head and neck squamous cell carcinoma cells, we found that the expression of RAR? increased in cells grown to high density. Real-time reverse-transcriptase polymerase chain reaction revealed that the isoform increased in these cells was RAR?1. Epigenetic modifications of this isoform were tested using combined bisulfite restriction analysis and chromatin immunoprecipitation assays. The UMSCC38 cell line showed significant RAR?1 expression (P < 0.001), which was dependent on cell density and culture duration. The increased expression of RARβ1 was not due to demethylation of its promoter. However, higher cell densities were associated with increased acetylation of histone 3 at lysine 9 in RARβ1 but not in RARβ2. These findings reveal that the expression of RARβ1 is regulated by cell density through changes in histone acetylation.
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.