Theillaumas Aurélie, Blanc Martine, Couderc Christophe, Poncet Gilles, Bazzi Wissam, Bernard Christine, Cordier-Bussat Martine, Scoazec Jean Yves, Roche Colette
Inserm, U865, IFR Lyon Est, Faculté Laënnec, 69372 Lyon Cedex 8, France.
Mol Cell Endocrinol. 2008 Sep 10;291(1-2):109-15. doi: 10.1016/j.mce.2008.05.019. Epub 2008 Jun 11.
In a previous study, we demonstrated that the Men1 gene is mainly expressed in the proliferative crypt compartment of the small intestine and that a reduction of menin expression in the crypt-like IEC-17 cell line induces an increase in proliferation rate concomitant with an increase in cyclin D1 expression. The aim of the present study was to test the hypothesis that the NF-kappaB pathway may be involved in cyclin D1 overexpression. Transcriptional activity of the cyclin D1 gene promoter was increased upon reduction of menin expression. Blockade of the NF-kappaB pathway restored proliferation, cell cycle, cyclin D1 gene transcription and cyclin D1 expression levels to those observed in the presence of menin. These data support a correlation between cyclin D1 expression, NF-kappaB activity and menin expression in this epithelial cell line and are relevant to the physiological function of menin in regulating proliferation in the intestinal epithelium.
在先前的一项研究中，我们证明Men1基因主要在小肠的增殖性隐窝区室中表达，并且在类隐窝IEC-17细胞系中menin表达的降低会导致增殖速率增加，同时细胞周期蛋白D1表达也增加。本研究的目的是检验NF-κB通路可能参与细胞周期蛋白D1过表达这一假说。menin表达降低时，细胞周期蛋白D1基因启动子的转录活性增加。NF-κB通路的阻断使增殖、细胞周期、细胞周期蛋白D1基因转录和细胞周期蛋白D1表达水平恢复到menin存在时所观察到的水平。这些数据支持了在该上皮细胞系中细胞周期蛋白D1表达、NF-κB活性和menin表达之间的相关性，并且与menin在调节肠上皮细胞增殖中的生理功能相关。
