Journal article
Essential requirement for β-arrestin2 in mouse intestinal tumors with elevated Wnt signaling
C Bonnans, M Flacelière, F Grillet, C Dantec, JP Desvignes, J Pannequin, D Severac, E Dubois, F Bibeau, V Escriou, P Crespy, L Journot, F Hollande, D Joubert
Proceedings of the National Academy of Sciences of the United States of America | NATL ACAD SCIENCES | Published : 2012
Abstract
β-Arrestins (Arrb) participate in the regulation of multiple signaling pathways, including Wnt/β-catenin, the major actor in human colorectal cancer initiation. To better understand the roles of Arrb in intestinal tumorigenesis, a reverse genetic approach (Arrb -/-) and in vivo siRNA treatment were used in Apc Δ14/+ mice. Mice with Arrb2 depletion (knockout and siRNA) developed only 33% of the tumors detected in their Arrb2-WT littermates, whereas Arrb1 depletion remained without significant effect. These remaining tumors grow normally and are essentially Arrb2-independent. Unsupervised hierarchical clustering analysis showed that they clustered with 25% of Apc Δ14/+;Arrb2 +/+ tumors. Genes ..
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Awarded by Association pour la Recherche contre le Cancer
Funding Acknowledgements
We thank Robert. J. Lefkowitz (Duke University Medical Center) for Arrb1<SUP>-/-</SUP> and Arrb2<SUP>-/-</SUP> mice and rabbit polyclonal anti-beta-arrestin (A1CT); Anne Cohen-Solal and Denis Greuet for excellent help in animal care and breeding; Joanne Ryan for her help in statistical analyses; Paul White and Florence Cabon for excellent advice on in vivo siRNA bio-distribution; Chantal Ripoll for her help in cryocut tissue sections; and Philippe Jay, Catherine Legraverend, and Joel Bockaert for scientific discussions and for comments on the manuscript. This work was supported by Grant 4996 from the Association pour la Recherche contre le Cancer and by Groupements des Entreprises Francaises dans la Lutte contre le Cancer.