Abstract
The protein products of the Dickkopf (DKK) genes are antagonists of Wnt glycoproteins, which participate in tumor development and progression by binding to frizzled receptors. In this study, the expression of DKKโ1 was analyzed in a panel of 43 human cultured carcinoma cell lines. DKKโ1 expression was consistently and significantly upregulated in pancreatic carcinoma cell lines. Low level of DKKโ3 expression was also seen. In contrast, the expression of DKKโ2 and โ4 was not detectable in most pancreatic carcinoma cell lines. The overexpression of DKKโ1 was confirmed in surgically resected human pancreatic cancer tissues, in which the mRNA level was evaluated in paired samples from cancerous and noncancerous pancreatic tissues. In ductal adenocarcinomas (23 cases), DKKโ1 mRNA levels were significantly upregulated compared to corresponding noncancerous tissues in a statistically significant level. To test the biological role of DKKโ1 in pancreatic carcinoma cells, we performed a knockdown of DKKโ1 in SUITโ2 human pancreatic adenocarcinoma cell line and S2โCP8, its metastatic subline, using a retroviral short hairpin RNA expression vector. DKKโ1 knockdown resulted in reduced migratory activity of SUITโ2 in vitro. The in vitro growth rate and Matrigel invasion were also suppressed by DKKโ1 knockdown in S2โCP8 cells. Collectively, the evidence suggests that, despite of its presumed antagonistic role in Wnt signaling, DKKโ1 may have a role in the aggressiveness of pancreatic carcinoma cells and could, therefore, serve as a novel biomarker of pancreatic cancer.