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Gene Review

WNT2  -  wingless-type MMTV integration site family...

Homo sapiens

Synonyms: INT1L1, IRP, Int-1-like protein 1, Int-1-related protein, Protein Wnt-2
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Disease relevance of WNT2


Psychiatry related information on WNT2


High impact information on WNT2

  • Important questions that remain unsolved include the identity of the vertebrate IRP that triggers the apoptotic cascade and the identities of the crucial substrates whose cleavage results in the dramatic morphological changes during apoptosis [5].
  • Our results identify a regulatory link between energy and iron metabolism in vertebrates and invertebrates, and suggest biological functions for the IRE/IRP regulatory system in addition to the maintenance of iron homeostasis [6].
  • Differences in the two binding sites may be important in the function of the IRE-IRP regulatory system [7].
  • Recombinations between IRP and cystic fibrosis [8].
  • DNA sequences from the IRP locus that recognize RFLPs are proving to be highly informative for prenatal diagnosis [8].

Chemical compound and disease context of WNT2


Biological context of WNT2


Anatomical context of WNT2


Associations of WNT2 with chemical compounds

  • WNT2 is an evolutionarily conserved secreted-type glycoprotein belonging to the WNT family [2].
  • WNT2B2, but not WNT2 and WNT2B1, was expressed in MCF-7 cells. beta-estradiol (100 nM) induced a transient up-regulation of WNT2 in MCF-7 cells, and also induced down-regulation of WNT2B2 [3].
  • Retinoic acid (10 microM) induced a transient up-regulation of WNT2 in NT2 cells [3].
  • We then assessed the antiproliferative effects of the Wnt2 antibody and Alimta, one of the current standard treatments of MPM [14].
  • However, despite the far greater Fe chelation efficacy of 311 compared with DFO, a similar increase in IRP-RNA binding activity occurred after 2 to 4 hours of incubation with either chelator, and the binding activity was not inhibited by cycloheximide [15].

Physical interactions of WNT2

  • Here, we showed that three potential AS-IREs, i.e. AS-IRE1, 4, and 5, derived from HER-2/neu antisense sequence could bind endogenous iron regulatory protein (IRP) and, when placed in 5' untranslated region (5'UTR) of a reporter gene, the gene expression could be translationally repressed by recombinant IRP in vitro [16].
  • Purified human brain IRP protein has a molecular mass of approximately 100 kDa and is capable of forming two RNA-protein complexes with ferritin IRE RNA and reacts strongly with IRP1 antiserum [17].

Other interactions of WNT2

  • We genotyped all four WNT2 polymorphisms and a polymorphic trinucleotide repeat in the 5' UTR of RELN in 107 families with multiple autistic children, and evaluated evidence for association between these variants and autism by the transmission disequilibrium test (TDT) [11].
  • In conclusion, (1) alterations of key regulators of the Wnt signaling are frequent in the pathogenesis of BE; (2) the APC and SFRP1 genes are inactivated by promoter methylation in BE; (3) the WNT2 gene is upregulated along the progression from low-grade dysplasia to EAC [18].
  • Synchronous up-regulation of FZD10 and WNT2 mRNAs might lead to activation of the WNT signaling pathway in human breast cancer [19].
  • Our data demonstrate that TNF-alpha may exert its effect by inhibiting IR autophosphorylation in HAEC and also by reducing IR protein (IRP) expression [20].
  • Of these four presumably activated oncogenes, two, MYCN and WNT2, were previously not assumed to play a pathogenic role in stomach cancer [21].

Analytical, diagnostic and therapeutic context of WNT2


  1. Expression and regulation of WNT5A and WNT5B in human cancer: up-regulation of WNT5A by TNFalpha in MKN45 cells and up-regulation of WNT5B by beta-estradiol in MCF-7 cells. Saitoh, T., Katoh, M. Int. J. Mol. Med. (2002) [Pubmed]
  2. WNT2 and human gastrointestinal cancer (review). Katoh, M. Int. J. Mol. Med. (2003) [Pubmed]
  3. Differential regulation of WNT2 and WNT2B expression in human cancer. Katoh, M. Int. J. Mol. Med. (2001) [Pubmed]
  4. No association between the WNT2 gene and autistic disorder. McCoy, P.A., Shao, Y., Wolpert, C.M., Donnelly, S.L., Ashley-Koch, A., Abel, H.L., Ravan, S.A., Abramson, R.K., Wright, H.H., DeLong, G.R., Cuccaro, M.L., Gilbert, J.R., Pericak-Vance, M.A. Am. J. Med. Genet. (2002) [Pubmed]
  5. ICE-related proteases in apoptosis. Takahashi, A., Earnshaw, W.C. Curr. Opin. Genet. Dev. (1996) [Pubmed]
  6. Translational regulation of mammalian and Drosophila citric acid cycle enzymes via iron-responsive elements. Gray, N.K., Pantopoulos, K., Dandekar, T., Ackrell, B.A., Hentze, M.W. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  7. Differences in the RNA binding sites of iron regulatory proteins and potential target diversity. Butt, J., Kim, H.Y., Basilion, J.P., Cohen, S., Iwai, K., Philpott, C.C., Altschul, S., Klausner, R.D., Rouault, T.A. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  8. Recombinations between IRP and cystic fibrosis. Farrall, M., Wainwright, B.J., Feldman, G.L., Beaudet, A., Sretenovic, Z., Halley, D., Simon, M., Dickerman, L., Devoto, M., Romeo, G. Am. J. Hum. Genet. (1988) [Pubmed]
  9. Remodeling the regulation of iron metabolism during erythroid differentiation to ensure efficient heme biosynthesis. Schranzhofer, M., Schifrer, M., Cabrera, J.A., Kopp, S., Chiba, P., Beug, H., Müllner, E.W. Blood (2006) [Pubmed]
  10. Molecular cloning and characterization of ST7R (ST7-like, ST7L) on human chromosome 1p13, a novel gene homologous to tumor suppressor gene ST7 on human chromosome 7q31. Katoh, M. Int. J. Oncol. (2002) [Pubmed]
  11. Lack of evidence for an association between WNT2 and RELN polymorphisms and autism. Li, J., Nguyen, L., Gleason, C., Lotspeich, L., Spiker, D., Risch, N., Myers, R.M. Am. J. Med. Genet. B Neuropsychiatr. Genet. (2004) [Pubmed]
  12. Evidence supporting WNT2 as an autism susceptibility gene. Wassink, T.H., Piven, J., Vieland, V.J., Huang, J., Swiderski, R.E., Pietila, J., Braun, T., Beck, G., Folstein, S.E., Haines, J.L., Sheffield, V.C. Am. J. Med. Genet. (2001) [Pubmed]
  13. Frequent up-regulation of WNT2 in primary gastric cancer and colorectal cancer. Katoh, M. Int. J. Oncol. (2001) [Pubmed]
  14. Wnt2 as a new therapeutic target in malignant pleural mesothelioma. Mazieres, J., You, L., He, B., Xu, Z., Twogood, S., Lee, A.Y., Reguart, N., Batra, S., Mikami, I., Jablons, D.M. Int. J. Cancer (2005) [Pubmed]
  15. The potential of iron chelators of the pyridoxal isonicotinoyl hydrazone class as effective antiproliferative agents III: the effect of the ligands on molecular targets involved in proliferation. Darnell, G., Richardson, D.R. Blood (1999) [Pubmed]
  16. Targeting HER-2/neu-overexpressing breast cancer cells by an antisense iron responsive element-directed gene expression. Li, Z., Xia, W., Fang, B., Yan, D.H. Cancer Lett. (2001) [Pubmed]
  17. Demonstration and characterization of the iron regulatory protein in human brain. Hu, J., Connor, J.R. J. Neurochem. (1996) [Pubmed]
  18. Alterations of the Wnt signaling pathway during the neoplastic progression of Barrett's esophagus. Clément, G., Braunschweig, R., Pasquier, N., Bosman, F.T., Benhattar, J. Oncogene (2006) [Pubmed]
  19. Up-regulation of Frizzled-10 (FZD10) by beta-estradiol in MCF-7 cells and by retinoic acid in NT2 cells. Saitoh, T., Mine, T., Katoh, M. Int. J. Oncol. (2002) [Pubmed]
  20. Tumor necrosis factor-alpha inhibits insulin-induced increase in endothelial nitric oxide synthase and reduces insulin receptor content and phosphorylation in human aortic endothelial cells. Aljada, A., Ghanim, H., Assian, E., Dandona, P. Metab. Clin. Exp. (2002) [Pubmed]
  21. Mapping of chromosomal imbalances in gastric adenocarcinoma revealed amplified protooncogenes MYCN, MET, WNT2, and ERBB2. Nessling, M., Solinas-Toldo, S., Wilgenbus, K.K., Borchard, F., Lichter, P. Genes Chromosomes Cancer (1998) [Pubmed]
  22. Genomic sequence analysis of Fugu rubripes CFTR and flanking genes in a 60 kb region conserving synteny with 800 kb of human chromosome 7. Davidson, H., Taylor, M.S., Doherty, A., Boyd, A.C., Porteous, D.J. Genome Res. (2000) [Pubmed]
  23. The Wnt pathway, epithelial-stromal interactions, and malignant progression in phyllodes tumours. Sawyer, E.J., Hanby, A.M., Rowan, A.J., Gillett, C.E., Thomas, R.E., Poulsom, R., Lakhani, S.R., Ellis, I.O., Ellis, P., Tomlinson, I.P. J. Pathol. (2002) [Pubmed]
  24. Hereditary hyperferritinemia-cataract syndrome: relationship between phenotypes and specific mutations in the iron-responsive element of ferritin light-chain mRNA. Cazzola, M., Bergamaschi, G., Tonon, L., Arbustini, E., Grasso, M., Vercesi, E., Barosi, G., Bianchi, P.E., Cairo, G., Arosio, P. Blood (1997) [Pubmed]
  25. Response of monocyte iron regulatory protein activity to inflammation: abnormal behavior in genetic hemochromatosis. Recalcati, S., Pometta, R., Levi, S., Conte, D., Cairo, G. Blood (1998) [Pubmed]
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