Biochemical and Biophysical Research Communications
Cloning and characterization of the promoter of human Wnt inhibitory factor-1
Section snippets
Materials and methods
Cell cultures. Human kidney transfected epithelial cell line (293T), human non-small-cell lung cancer cell line (NCI-A549), human colorectal cancer cell lines (HCT116 and SW480), which harbor mutations in CTNNB1 and APC, respectively [23], [5], and human mesothelioma cancer cell lines (H28, MS1) that lack β-catenin expression [12] were obtained from American Type Culture Collections (ATCC, Manassas, Virginia). These cells, except human kidney transfected epithelial cell line (293T), were
Identification of the WIF-1 promoter region
To identify the WIF-1 promoter, we conducted a BLAST search with the 1140-bp coding sequence of WIF-1 as a virtual probe against the human genomic database at the UCSC web server (http://genome.ucsc.edu/). We used a promoter search program (http://www.genomatix.de/) to confirm that the 5′ flanking region of the gene presents classical features of a promoter region (Fig. 1). Several important transcription sites were observed in this fragment such as Homobox Protein Engrailed (−826 to −830 from
Discussion
The Wnt pathway plays a significant role in carcinogenesis. It is well known that mutations in the adenomatous polyposis coli gene (APC), axin, or β-catenin lead to β-catenin accumulation in the nucleus which is often observed in human cancers [25]. Moreover, β-catenin does not bind to DNA itself, but needs to bind to TCF/LEF transcription factors for transactivation in the nucleus of a specific subset of genes [26], [27]. Although the intracytoplasmic Wnt pathway has been widely studied,
Acknowledgments
This work was supported by the Larry Hall memorial trust and the Kazan, McClain, Edises, Abrams, Fernandez, and Lyons & Farrise Foundation.
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