Cloning and characterization of the promoter of human Wnt inhibitory factor-1

• Published in: Biochemical and biophysical research communications 2004-10, Vol.323 (1), p.229-234
• Main Authors: Reguart, Noemi, He, Biao, Xu, Zhidong, You, Liang, Lee, Amie Y., Mazieres, Julien, Mikami, Iwao, Batra, Sonny, Rosell, Rafael, McCormick, Frank, Jablons, David M.
• Format: Article
• Language: English
• Subjects: Base Sequence; Cancer; Carrier Proteins - chemistry; Carrier Proteins - genetics; Carrier Proteins - physiology; Cell Line; Cell Line, Tumor; Cloning, Molecular; CpG Islands; Enzyme Activation; Extracellular Matrix Proteins; Humans; Intercellular Signaling Peptides and Proteins; Intracellular Signaling Peptides and Proteins; Ligands; Luciferase reporter; Luciferases - metabolism; Models, Genetic; Molecular Sequence Data; Promoter; Promoter Regions, Genetic; Repressor Proteins - chemistry; Repressor Proteins - genetics; Repressor Proteins - physiology; Signal Transduction; Transfection; WIF-1; Wnt/β-catenin signaling
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2004.08.075

Wnt inhibitory factor-1 (WIF-1) is a secreted antagonist of Wnt signaling and functions by directly binding to Wnt ligands in the extracellular space. Here we report the identification of the 5′ promoter region (∼1.5 kb) of the human WIF-1 gene. Functional analysis of this region shows that a whole fragment displays high basal promoter activity in different cell lines, while the truncated forms do not, indicating that integrity of the WIF-1 promoter region may be important for WIF-1 activity. Moreover, we found that the expression level of β-catenin in cancer cell lines correlates with the WIF-1 promoter activity, suggesting that the WIF-1 promoter may be regulated by the Wnt/β-catenin pathway and may function in a negative feedback manner. Our results also suggest that a methylated CpG island, which we observed recently in human lung cancer, lies within the functional WIF-1 promoter region and therefore bears the importance of the methylation-status of this CpG island as an important key in Wnt activation in human cancer.