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Wnt signaling activation and WIF-1 silencing in nasopharyngeal cancer cell lines
Authors:Lin Yu-Ching  You Liang  Xu Zhidong  He Biao  Mikami Iwao  Thung Elaine  Chou Josephine  Kuchenbecker Kristopher  Kim Jae  Raz Dan  Yang Cheng-Ta  Chen Jan-Kan  Jablons David M
Institution:Thoracic Oncology Laboratory, Department of Surgery, Comprehensive Cancer Center, University of California, San Francisco, CA 94115, USA.
Abstract:Aberrant activation of Wingless-type (Wnt) signaling pathway plays a critical role in oncogenesis of 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, we reported Wnt signaling in various human malignancies. In addition, we identified in lung cancer that WIF-1 is silenced due to promoter hypermethylation. In this study, we found constitutive activation of Wnt signaling and WIF-1 silencing in nasopharyngeal carcinoma (NPC) cell lines. Furthermore, by utilizing methylation-specific PCR and sequence analysis, we demonstrated that frequent hypermethylation of the WIF-1 promoter correlates with WIF-1 silencing in NPC cell lines. Our results indicate that aberrant Wnt signaling is a common event in NPC carcinogenesis linked with WIF-1 silencing in at least cell lines. Strategies targeting these molecules should be potentially promising in treating NPC.
Keywords:Wnt inhibitory factor-1  Wnt signaling  Promoter hypermethylation  Nasopharyngeal carcinoma  Transfection
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