WNT2 and human gastrointestinal cancer (review).
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.
Katoh
Masaru
M
Genetics and Cell Biology Section, Genetics Division, National Cancer Center Research Institute, Chuo-ku, Tokyo 104-0045, Japan. mkatoh@ncc.go.jp
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
D011518:Proto-Oncogene Proteins; C495244:WNT2 protein, human; D051153:Wnt Proteins; D051154:Wnt2 Protein