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

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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.