Abstract 4993: IFI27 and NOV, downstream regulated genes by S100A4, are playing important roles in pancreatic carcinogenesis

S100A4 is a member of the Ca 2+ -dependent S100 protein family, and positive association between S100A4-upregulation andmetastasis/invasion was reported. We reported a significant association between upregulation of S100A4 and perineural invasion in pancreatic cancer. Furthermore, siRNA-mediated knockdown of S100A4 promoted cell death mainly mediated by induction of apoptosis only in cancer cells with high expression of S100A4, and forced expression of S100A4 induced accelerated cell motility only in cancer cells with low expression. To explore the molecular mechanisms of cell motility after the forced expression of S100A4, we analyzed gene expression profiles and identified some candidate genes including IFI27 and NOV (CCN3) that are regulated by S100A4-upregulation, and we further focused on IFI27 and NOV. IFI27 showed significant upregulation after the forced expression of S100A4 and downregulation after siRNA mediated knockdown of S100A4, while NOV seemed to show an inverse relationship with S100A4. Using 93 primary resected tumors, we performed immunohistochemical analyses and identified significant positive association between S100A4 and IFI27 expressions. Although NOV did not show significant inverse-association, siRNA-mediated knockdown in high level expressing cells showed significant acceleration of cell motility. Clinicopathologic characteristics demonstrated positive associations between IFI27 expression and intrapancreatic neural invasion (P=0.0023) and negative associations between NOV expression and invasion pattern (P=0.017) were observed. Our present study suggests that IFI27 and NOV may be downstream regulated genes of S100A4 and that expressional changes may play important roles in invasion of pancreatic cancer. Citation Format: Na Chen, Yuriko Saiki, Hitoshi Sekine, Makoto Sunamura, Shinichi Fukushige, Fuyuhiko Motoi, Shinichi Egawa, Michiaki Unno, Akira Horii. IFI27 and NOV , downstream regulated genes by S100A4, are playing important roles in pancreatic carcinogenesis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4993. doi:10.1158/1538-7445.AM2014-4993