PUBLICATION
Retinoic Acid Inhibits β-Catenin through Suppression of Cox-2: A role for truncated adenomatous polyposis coli
- Authors
- Eisinger, A.L., Nadauld, L.D., Shelton, D.N., Prescott, S.M., Stafforini, D.M., and Jones, D.A.
- ID
- ZDB-PUB-070806-31
- 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.
Citation
Eisinger, A.L., Nadauld, L.D., Shelton, D.N., Prescott, S.M., Stafforini, D.M., and Jones, D.A. (2007) Retinoic Acid Inhibits β-Catenin through Suppression of Cox-2: A role for truncated adenomatous polyposis coli. The Journal of biological chemistry. 282(40):29394-29400.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping