並列タイトル等エナメル上皮腫由来細胞の レチノイン酸作用時における遺伝子解析
一般注記Ameloblastoma is one of the most common odontogenic benign tumors in the jawbone, and may recur because it grows in a locally invasive manner. Although many studies have been performed on ameloblastoma, its bioactive characteristics remain unclear.Retinoic acid, a metabolite of fat-soluble vitamin A used as a leukemia drug, has been demonstrated to have antitumor effects on some tumor types. The present study examined whether retinoic acid has potential as a new therapeutic drug for ameloblastoma. We found that retinoic acid 1) inhibited the proliferation of cells derived from ameloblastoma and 2) induced differentiation. However, its intracellular signaling and regulatory mechanisms remain unclear. In this study, we primarily cultured cells from ameloblastoma to elucidate signal transduction, and examined the differences in gene expression levels due to retinoic acid action by microarray analysis.Surgically removed specimens were obtained with consent from the Second Department of Oral and Maxillofacial Surgery, Osaka Dental University Hospital. Primary culture was started with medium for the epithelium, followed by cloning to be used as ameloblastoma cells. Subsequently, retinoic acid was added at a final concentration of 10-6 to 10-7 M and incubated for 6 hours to prepare an experimental group. A control group was also prepared without its addition. After culturing, the cells were collected to extract RNA from each group for microarray analysis.In the experimental group, the expression of the EDF1 gene was most strongly increased, whereas that of the TM4SF10 gene was mostly markedly suppressed. Furthermore, the expression levels of the MMP3 and FGF2 genes were suppressed by 0.37- and 0.48-fold, respectively.The regulation of cell growth and differentiation comprises comprehensive regulatory mechanisms, such as protein synthesis, degradation, complex formation, and phosphorylation, in addition to gene expression. Our study suggested that changes in the expression of FGF2 and MMP3 genes are partly involved in the inhibition of growth and promotion of differentiation by retinoic acid in ameloblastoma-derived cells.
2019年度
連携機関・データベース国立情報学研究所 : 学術機関リポジトリデータベース(IRDB)(機関リポジトリ)