Department of Rehabilitation, Kobe International University, 9-1-6 Koyocho-Naka, Higashinada, Kobe, Hyogo 658-0032, Japan.
Biochem Biophys Res Commun. 2011 Jul 15;410(4):798-802. doi: 10.1016/j.bbrc.2011.06.066. Epub 2011 Jun 15.
Pre-B-cell leukemia transcription factor (PBX)/three-amino-acid loop extension (TALE) class transcription factors [PBX1-4, Meis homeobox (Meis) 1-3, pbx/knotted 1 homeobox (Prep) 1, 2] are involved in tumorigenesis and metastasis. To investigate further the function of PBX/TALE class transcription factors, mRNA expression profile after downregulation of each mRNA expression by siRNA transfection in pancreatic cancer cell line, Panc-1, was examined. Downregulation of Meis1 resulted in downregulation of mitochondrial genes, but those of PBX1 and PBX2 did not. Quantitative reverse transcription polymerase chain reaction confirmed downregulation of mitochondrial genes by Meis1 siRNA transfection. Chromatin immunoprecipitation assay revealed the binding of Meis1 to the mitochondrial promoter region that contained the putative Meis1 binding site. Luciferase reporter assay showed the increase of luciferase activity of a construct containing the Meis1 binding site compared with that with shorter fragment without Meis1 binding region. These findings indicate that Meis1 works as a transcription factor for mitochondrial genes in pancreatic cancer cells.
前期 B 细胞白血病转录因子 (PBX)/三氨基酸环延伸 (TALE) 类转录因子 [PBX1-4、Meis 同源盒 (Meis) 1-3、pbx/结节 1 同源盒 (Prep) 1、2] 参与肿瘤发生和转移。为了进一步研究 PBX/TALE 类转录因子的功能，通过 siRNA 转染下调胰腺癌细胞系 Panc-1 中的每种 mRNA 表达，检查了 mRNA 表达谱。下调 Meis1 导致线粒体基因下调，但 PBX1 和 PBX2 则没有。定量逆转录聚合酶链反应证实了 Meis1 siRNA 转染导致线粒体基因下调。染色质免疫沉淀分析显示 Meis1 与包含推定 Meis1 结合位点的线粒体启动子区域结合。荧光素酶报告基因分析显示，包含 Meis1 结合位点的构建体的荧光素酶活性与没有 Meis1 结合区的较短片段相比增加。这些发现表明 Meis1 在胰腺癌细胞中作为线粒体基因的转录因子发挥作用。
