Loss of β-catenin in adrenocortical cancer cells causes growth inhibition and reversal of epithelial-to-mesenchymal transition

摘要: // Aude Salomon 1, 2, 3 , Michelle Keramidas Cecile Maisin Michael Thomas 1 Institut National de la Sante et Recherche Medicale, Unite 1036, Grenoble, France 2 Commissariat a l’Energie Atomique, Institute of Life Sciences Research and Technologies, Biology Cancer Infection, Universite Grenoble Alpes, Mixte Recherche-S1036, Correspondence to: Thomas, e-mail: michael.thomas@cea.fr Keywords: adrenocortical carcinoma, β-catenin, shRNA, epithelial-mesenchymal transition Received: December 02, 2014      Accepted: January 26, 2015      Published: March 18, 2015 ABSTRACT Adrenal carcinoma (ACC) is rare neoplasm with poor outcome. Aberrant expression β-catenin has been found in approximatively 30% ACC. We herein studied its effects on the growth human ACC cell line H295R. The cells were infected short hairpin RNA (shRNA)-mediated silencing β-catenin. Two shRNAs used induced down-regulation protein levels. these decreased increased H295R S G /M phases. This cytostatic effect due to decrease phosphorylated MAPK an up-regulation cyclin-dependent kinase inhibitors p57 KIP2 p21 CIP p27 KIP1 . In addition, knockdown Akt apoptosis. Finally, loss was sufficient induce reversal epithelial-to-mesenchymal transition. then transplanted genetically modified Scid mice. Tumor suppression achieved by two showing vitro efficacy. Proliferation not reduced silenced tumors. contrast, p57, proteins expressed at high levels tumors along increase apoptotic cells. These findings indicate that inhibits tumor inducing transcriptional functional changes.