| Summary: | 博士 === 長庚大學 === 臨床醫學研究所 === 96 === Silencing of Wnt antagonists with aberrant activation of Wnt signaling is a common phenomenon in various human cancers. Wnt inhibitory factor-1 (WIF-1) is a secreted antagonist of Wnt signaling and acts through direct binding to Wnt in the extracellular space. Recently, WIF-1 silencing due to promoter hypermethylation in non-small cell lung cancer (NSCLC) has been reported. In this study, we tried to illustrate the impact of WIF-1 gene expression in NPC and melanoma with WIF-1 silencing by in vitro and in vivo studies. Re-expression of WIF-1 by non-viral gene transfer with a pcDNA3.1 vector inhibited cancer cells growth in vitro. Additionally, the inhibitory effect was related to down-regulation of Wnt signaling which was demonstrated at both the transcriptional and translational levels. Furthermore, by utilizing a xenograft mouse model, we confirmed the effect of WIF-1 expression in suppressing tumor growth by inhibition of Wnt signaling in vivo.
In addition, we studied the WIF-1 promoter hypermethyation in malignant pleural effusions (MPE) of NSCLC and found MSP were positive in 25 (69.4%) of 36 NSCLC patients with malignant pleural effusion. In contrast, the results of WIF-1 promoter region MSP were negative in all 35 patients with pleural effusion of benign origin. The age, gender, and smoking status of patients were not correlated with the WIF-1 promoter MSP.
Taken together, WIF-1 may be of potential in developing novel therapeutics and diagnostic tools for various human cancers.
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