Department of Biochemistry, School of Medicine, Chang-Gung University, 259 Wen-hwa 1 Road, Taoyuan, 333, Taiwan, ROC.
Cell Mol Life Sci. 2010 Jun;67(11):1831-43. doi: 10.1007/s00018-010-0281-2. Epub 2010 Feb 10.
The thyroid hormone T(3) regulates differentiation, growth, and development. We demonstrated that methionine adenosyltransferase 1A (MAT1A) was positively regulated by T(3) identified by cDNA microarray previously. The expression of the MAT1A was upregulated by T(3) in hepatoma cell lines overexpressing thyroid hormone receptors (TRs). Additionally, these findings indicate that MAT1A may be regulated by CCAAT/enhancer binding protein (C/EBP). The critical role of the C/EBP binding sites was confirmed by the reporter or chromatin immuno-precipitation (ChIP) assay. In addition, C/EBP was upregulated in hepatoma cells after T(3) treatment and ectopic expression of MAT1A inhibited cell migration and invasion in J7 hepatoma cells. Conversely, knockdown of MAT1A expression increased cell migration. Together, these findings suggest that the expression of the MAT1A gene is mediated by C/EBP and is indirectly upregulated by T(3). Finally, TR was downregulated in a small subset of hepatocellular carcinoma cells concomitantly reduced the expression of C/EBPalpha and MAT1A.
甲状腺激素 T(3) 调节分化、生长和发育。我们之前通过 cDNA 微阵列证实，蛋氨酸腺苷转移酶 1A (MAT1A) 受 T(3) 正向调控。在过表达甲状腺激素受体 (TR) 的肝癌细胞系中，T(3) 上调了 MAT1A 的表达。此外，这些发现表明 MAT1A 可能受 CCAAT/增强子结合蛋白 (C/EBP) 调控。通过报告基因或染色质免疫沉淀 (ChIP) 分析证实了 C/EBP 结合位点的关键作用。此外，T(3)处理后肝癌细胞中 C/EBP 上调，MAT1A 的异位表达抑制 J7 肝癌细胞的迁移和侵袭。相反，MAT1A 表达的下调增加了细胞迁移。综上所述，这些发现表明 MAT1A 基因的表达受 C/EBP 介导，并间接受 T(3)上调。最后，TR 在一小部分肝癌细胞中下调，同时降低了 C/EBPalpha 和 MAT1A 的表达。
