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ZFIN ID: ZDB-PUB-070806-31
Retinoic Acid Inhibits β-Catenin through Suppression of Cox-2: A role for truncated adenomatous polyposis coli
Eisinger, A.L., Nadauld, L.D., Shelton, D.N., Prescott, S.M., Stafforini, D.M., and Jones, D.A.
Date: 2007
Source: The Journal of biological chemistry 282(40): 29394-29400 (Journal)
Registered Authors:
Keywords: none
MeSH Terms:
  • Adenomatous Polyposis Coli/metabolism*
  • Animals
  • Cyclooxygenase 2/metabolism*
  • Dinoprostone/metabolism
  • Down-Regulation
  • Gene Expression Regulation*
  • Immunoblotting
  • In Situ Hybridization
  • Mutation*
  • RNA/metabolism
  • Signal Transduction
  • Tretinoin/pharmacology*
  • Zebrafish
  • beta Catenin/antagonists & inhibitors
  • beta Catenin/metabolism*
PubMed: 17673467 Full text @ J. Biol. Chem.
Mutations in adenomatous polyposis coli (APC) underlie the earliest stages of colorectal carcinogenesis. Consequences of APC mutation include stabilization of ss-catenin, dysregulation of cyclooxygenase-2 (COX-2) expression and loss of retinoic acid production, events with poorly defined interactions. Here, we show that treatment of zebrafish expressing a truncated form of Apc with either retinoic acid or a selective Cox-2 inhibitor decreased beta-catenin protein levels and downstream signaling events. Interestingly, the destruction of beta-catenin in apc mutant embryos following Cox-2 inhibition required the presence of truncated Apc. These findings support roles for retinoic acid and Cox-2 in regulating the stability of beta-catenin following Apc loss. Furthermore, truncated Apc appears to retain the ability to target beta-catenin for destruction, but only in the absence of COX-2 activity. This novel function of truncated Apc may provide a molecular basis for the efficacy of COX-2 inhibitors in the treatment of colon cancer.