Asbestos Research Today is a free monthly online journal that collates and summarizes the latest research about Asbestos, including details on mesothelioma, lung disease, dangers, effects, risks.

Dickkopf-1 antagonizes Wnt signaling independent of beta-catenin in human mesothelioma.

Lee AY, He B, You L, Xu Z, Mazieres J, Reguart N, Mikami I, Batra S, Jablons DM

Thoracic Oncology Laboratory, Department of Surgery, Comprehensive Cancer Center, University of California, San Francisco, CA 94115, USA.

Dickkopf-1 (Dkk-1) is a secreted protein that acts as a potent inhibitor of the Wnt signal transduction pathway. It is thought that the antagonistic effect of Dkk-1 is specific to the canonical (Wnt/beta-catenin) pathway. In this study, we demonstrate that restoration of Dkk-1 expression suppresses cell growth and induces apoptotic cell death in beta-catenin-deficient mesothelioma cell lines H28 and MS-1. Furthermore, we found that a small-molecule inhibitor of JNK inhibited the apoptosis induced by Dkk-1 overexpression in these cells. Together, our data suggest that Dkk-1 may be able to antagonize Wnt signaling and exert its tumor suppressive effects through beta-catenin-independent non-canonical pathways (i.e., the Wnt/JNK pathway).

Published 28 September 2004 in Biochem Biophys Res Commun, 323(4): 1246-50.
Full-text of this article is available online (may require subscription).

© 2004-2008 Asbestos Research Today. All Rights Reserved.