Canonical WNT signaling pathway and human AREG

  • Authors:
    • Yuriko Katoh
    • Masaru Katoh
  • View Affiliations

  • Published online on: June 1, 2006     https://doi.org/10.3892/ijmm.17.6.1163
  • Pages: 1163-1166
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Abstract

AREG (Amphiregulin), BTC (β-cellulin), EGF, EPGN (Epigen), EREG (Epiregulin), HBEGF, NRG1, NRG2, NRG3, NRG4 and TGFA (TGFα) constitute EGF family ligands for ERBB family receptors. Cetuximab (Erbitux), Pertuzumab (Omnitarg) and Trastuzumab (Herceptin) are anti-cancer drugs targeted to EGF family ligands, while Gefitinib (Iressa), Erlotinib (Tarceva) and Lapatinib (GW572016) are anti-cancer drugs targeted to ERBB family receptors. AREG and TGFA are biomarkers for Gefitinib non-responders. The TCF/LEF binding sites within the promoter region of human EGF family members were searched for by using bioinformatics and human intelligence (Humint). Because three TCF/LEF-binding sites were identified within the 5'-promoter region of human AREG gene, comparative genomics analyses on AREG orthologs were further performed. The EPGN-EREG-AREG-BTC cluster at human chromosome 4q13.3 was linked to the PPBP-CXCL segmental duplicons. AREG was the paralog of HBEGF at human chromosome 5q31.2. Chimpanzee AREG gene, consisting of six exons, was located within NW_105918.1 genome sequence. Chimpanzee AREG was a type I transmembrane protein showing 98.0% and 71.4% total amino-acid identity with human AREG and mouse Areg, respectively. Three TCF/LEF-binding sites within human AREG promoter were conserved in chimpanzee AREG promoter, but not in rodent Areg promoters. Primate AREG promoters were significantly divergent from rodent Areg promoters. AREG mRNA was expressed in a variety of human tumors, such as colorectal cancer, liver cancer, gastric cancer, breast cancer, prostate cancer, esophageal cancer and myeloma. Because human AREG was characterized as potent target gene of WNT/β-catenin signaling pathway, WNT signaling activation could lead to Gefitinib resistance through AREG upregulation. AREG is a target of systems medicine in the field of oncology.

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June 2006
Volume 17 Issue 6

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Katoh Y and Katoh M: Canonical WNT signaling pathway and human AREG. Int J Mol Med 17: 1163-1166, 2006.
APA
Katoh, Y., & Katoh, M. (2006). Canonical WNT signaling pathway and human AREG. International Journal of Molecular Medicine, 17, 1163-1166. https://doi.org/10.3892/ijmm.17.6.1163
MLA
Katoh, Y., Katoh, M."Canonical WNT signaling pathway and human AREG". International Journal of Molecular Medicine 17.6 (2006): 1163-1166.
Chicago
Katoh, Y., Katoh, M."Canonical WNT signaling pathway and human AREG". International Journal of Molecular Medicine 17, no. 6 (2006): 1163-1166. https://doi.org/10.3892/ijmm.17.6.1163