title: WNT2 and human gastrointestinal cancer (review).
abstract: WNT2 gene on human chromosome 7q31 is a paralog of the WNT2B gene on human chromosome 1p13. Rat Wnt2 gene was identified within rat genome draft sequence AC095247.4. Human WNT2 showed 96.4% total-amino-acid identity with rat Wnt2, 96.1% with mouse Wnt2, 68.6% with zebrafish wnt2, and 67.8% with fugu wnt2. WNT2 is an evolutionarily conserved secreted-type glycoprotein belonging to the WNT family. WNT2 mRNA is expressed in human fetal lung and placenta, but almost undetectable in normal gastrointestinal tract. WNT2 mRNA is frequently up-regulated in human gastric cancer due to tumor-stromal interaction, and WNT2 gene is rarely amplified in human gastric cancer. WNT2 mRNA is also frequently up-regulated in colorectal polyps, primary colorectal cancer of stage A-C, and also in liver metastasis from colorectal cancer. Putative biding sites for estrogen receptor, GATA-1, AP-2, TCF-1, BHLH, MBF-I, p53, and HNF-5 are located within the 5'-flanking region of human WNT2 gene. WNT2 is up-regulated by beta-estradiol in human MCF-7 cells; however, the mechanism of WNT2 up-regulation in most cases of gastrointestinal cancer remains to be elucidated. WNT2 is a tumor marker of gastric and colorectal cancer. Detection of theWNT2 protein in feces by immunohistochemistry or ELISA and WNT2 mRNA in feces by cDNA-PCR or custom-made microarray could be applied for screening of colorectal cancer. Because WNT2 up-regulation leads to carcinogenesis through activation of the WNT-beta-catenin pathway, WNT2 specific antagonist might be applied for chemoprevention or treatment of gastrointestinal cancer. WNT2 gene is one of the targets for pharmacogenomics in the field of oncology.
authors.affiliation: Genetics and Cell Biology Section, Genetics Division, National Cancer Center Research Institute, Chuo-ku, Tokyo 104-0045, Japan. mkatoh@ncc.go.jp
authors.forename: Masaru
authors.initials: M
authors.lastname: Katoh
mesh_terms: D000818:Animals; D019143:Evolution, Molecular; D005770:Gastrointestinal Neoplasms / Q000235:genetics* / Q000378:metabolism*; D005826:Genetics, Medical; D023281:Genomics; D006801:Humans; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction; D051153:Wnt Proteins; D051154:Wnt2 Protein
chemical_list: D011518:Proto-Oncogene Proteins; C495244:WNT2 protein, human; D051153:Wnt Proteins; D051154:Wnt2 Protein