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Human Gene Therapy
Wnt Inhibitory Factor-1 Gene Transfer Inhibits Melanoma Cell Growth

To cite this article:
Yu-Ching Lin, Liang You, Zhidong Xu, Biao He, Cheng-Ta Yang, Jan-Kan Chen, Iwao Mikami, Geneviève Clément, Yihui Shi, Kristopher Kuchenbecker, Junichi Okamoto, Mohammed Kashani-Sabet, David M. Jablons. Human Gene Therapy. April 2007, 18(4): 379-386. doi:10.1089/hum.2006.005.

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Yu-Ching Lin 
Thoracic Oncology Laboratory, Department of Surgery, University of California, San Francisco, San Francisco, CA 94115.
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan 613.
Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan 333.
Liang You 
Thoracic Oncology Laboratory, Department of Surgery, University of California, San Francisco, San Francisco, CA 94115.
Zhidong Xu 
Thoracic Oncology Laboratory, Department of Surgery, University of California, San Francisco, San Francisco, CA 94115.
Biao He 
Thoracic Oncology Laboratory, Department of Surgery, University of California, San Francisco, San Francisco, CA 94115.
Cheng-Ta Yang 
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan 613.
Department of Respiratory Care, College of Medicine, Chang Gung University, Taoyuan, Taiwan 333.
Jan-Kan Chen 
Department of Physiology and Pharmacology, College of Medicine, Chang Gung University, Taoyuan, Taiwan 333.
Iwao Mikami 
Thoracic Oncology Laboratory, Department of Surgery, University of California, San Francisco, San Francisco, CA 94115.
Geneviève Clément 
Thoracic Oncology Laboratory, Department of Surgery, University of California, San Francisco, San Francisco, CA 94115.
Yihui Shi 
Thoracic Oncology Laboratory, Department of Surgery, University of California, San Francisco, San Francisco, CA 94115.
Kristopher Kuchenbecker 
Thoracic Oncology Laboratory, Department of Surgery, University of California, San Francisco, San Francisco, CA 94115.
Junichi Okamoto 
Thoracic Oncology Laboratory, Department of Surgery, University of California, San Francisco, San Francisco, CA 94115.
Mohammed Kashani-Sabet 
Auerback Melanoma Research Laboratory, Melanoma Center and Department of Dermatology, and Cutaneous Oncology Program, Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94115.
David M. Jablons 
Thoracic Oncology Laboratory, Department of Surgery, University of California, San Francisco, San Francisco, CA 94115.

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. In this study, we tried to illuminate the impact of WIF-1 gene expression in melanoma with WIF-1 silencing by in vitro and in vivo studies. We restored the expression of WIF-1 by nonviral gene transfer with a pcDNA3.1 vector. We demonstrated inhibition of melanoma cell growth after WIF-1 restoration in colony formation and proliferation assays in vitro. In addition, the inhibitory effect was related to downregulation of Wnt signaling, which was demonstrated at both the transcriptional and translational levels. Furthermore, by using a xenograft mouse model, we confirmed the effect of WIF-1 expression in suppressing tumor growth by inhibition of Wnt signaling in vivo. Our results suggest the potential for further application of WIF-1 gene therapy in melanoma with WIF-1 silencing.

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