title: Cloning and characterization of the promoter of human Wnt inhibitory factor-1.
abstract: 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 (approximately 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 beta-catenin in cancer cell lines correlates with the WIF-1 promoter activity, suggesting that the WIF-1 promoter may be regulated by the Wnt/beta-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.
authors.affiliation: Thoracic Oncology Laboratory, Department of Surgery, Comprehensive Cancer Center University of California, San Francisco, CA 94115, USA.
authors.forename: Noemi
authors.initials: N
authors.lastname: Reguart
authors.forename: Biao
authors.initials: B
authors.lastname: He
authors.forename: Zhidong
authors.initials: Z
authors.lastname: Xu
authors.forename: Liang
authors.initials: L
authors.lastname: You
authors.forename: Amie Y
authors.initials: AY
authors.lastname: Lee
authors.forename: Julien
authors.initials: J
authors.lastname: Mazieres
authors.forename: Iwao
authors.initials: I
authors.lastname: Mikami
authors.forename: Sonny
authors.initials: S
authors.lastname: Batra
authors.forename: Rafael
authors.initials: R
authors.lastname: Rosell
authors.forename: Frank
authors.initials: F
authors.lastname: McCormick
authors.forename: David M
authors.initials: DM
authors.lastname: Jablons
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D001483:Base Sequence; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D002460:Cell Line; D045744:Cell Line, Tumor; D003001:Cloning, Molecular; D018899:CpG Islands; D004789:Enzyme Activation; D016326:Extracellular Matrix Proteins; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D008156:Luciferases / Q000378:metabolism; D008957:Models, Genetic; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D015398:Signal Transduction; D014162:Transfection
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D016326:Extracellular Matrix Proteins; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D012097:Repressor Proteins; C118544:Wif1 protein, mouse; D008156:Luciferases