Vitamin A Research Today is a free monthly online journal that collates and summarizes the latest research about Vitamin A, including details on retinol, benefits, dosage, supplements, deficiency, information.

Retinoic acid inhibits beta-catenin through suppression of Cox-2: a role for truncated adenomatous polyposis coli.

Eisinger AL, Nadauld LD, Shelton DN, Prescott SM, Stafforini DM, Jones DA

Department of Oncological Sciences, University of Utah, Salt Lake City, Utah 84112, USA.

Mutations in adenomatous polyposis coli (APC) underlie the earliest stages of colorectal carcinogenesis. Consequences of APC mutation include stabilization of beta-catenin, dysregulation of cyclooxygenase-2 (COX-2) expression, and loss of retinoic acid production, events with poorly defined interactions. Here we showed 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.

Published 1 October 2007 in J Biol Chem, 282(40): 29394-400.
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