Analysis of the cell growth mechanism by ZIC2 transcription factor in pancreatic cancer cells.

ZIC2是ZIC家族中对中枢神经系统发育至关重要的5个基因之一。最近，我们发现ZIC2是一个独特的成员，在我们测试的所有（11/11）胰腺导管腺癌（PDAC）细胞系中表达。通过cDNA表达芯片分析，我们确定了ANXA8和FGFR3作为ZIC2的转录靶点。此外，我们发现强迫表达ANXA8减少了ZIC2敲低的PDAC细胞的凋亡细胞死亡，ZIC2以依赖于FGFR3的方式加速了ERK的磷酸化。虽然ZIC2、ANXA8和FGFR3的表达在正常胰管中免疫组织化学检测水平较低，但它们在PanIN和PDAC细胞中的表达显著。我们的体外和体内实验结果表明，ZIC2-ANXA8和ZIC2-FGFR3-ERK轴是PDAC发育过程中调控细胞凋亡和细胞增殖的重要信号通路。

ZIC2 is one of five members of ZIC family gene those are indispensable for the development of central nervous system. Recently, we uncovered that ZIC2 is a unique member which is expressed in all (11/11) of the pancreatic ductal adenocarcinoma (PDAC) cell lines we tested.From the cDNA expression microarray analysis, we identified ANXA8 and FGFR3 as ZIC2 transcriptional targets. Furthermore, we uncovered that forced expression of ANXA8 reduced the apoptotic cell death of the ZIC2-knockdown PDAC cells and that ZIC2 accelerated ERK phosphorylation in FGFR3 dependent manner. Although ZIC2, ANXA8 and FGFR3 expressions were immunohistochemically under-detectable levels in the normal pancreatic duct, their expression was prominent in PanIN and PDAC cells.Our in vitro and in vivo experimental results indicate that ZIC2-ANXA8 and ZIC2-FGFR3-ERK axis are important signaling pathways for the regulation of apoptosis and cell proliferation in the PDAC development.