Cloning and characterization of the promoter of human Wnt inhibitory factor-1.
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.
Reguart
Noemi
N
Thoracic Oncology Laboratory, Department of Surgery, Comprehensive Cancer Center University of California, San Francisco, CA 94115, USA.
He
Biao
B
Xu
Zhidong
Z
You
Liang
L
Lee
Amie Y
AY
Mazieres
Julien
J
Mikami
Iwao
I
Batra
Sonny
S
Rosell
Rafael
R
McCormick
Frank
F
Jablons
David M
DM
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
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