Protein Kinase C Epsilon and Genetic Networks in Osteosarcoma Metastasis

• Main Author: Goudarzi, Atta
• Other Authors: Andrulis, Irene
• Language: en_ca
• Published: 2012
• Subjects: osteosarcoma; metastasis; network analysis; 0715; 0369; 0307
• Online Access: http://hdl.handle.net/1807/33223

Pulmonary metastasis is the most frequent cause of osteosarcoma (OS) mortality. The aim of this study was to discover and characterize genetic networks differentially expressed in metastatic OS. Supervised network analysis of OS expression profiles was performed to discover genetic networks differentially activated or organized in metastatic OS. Broad trends among the profiles of metastatic tumours included aberrant activity of intracellular organization and translation networks, as well as disorganization of metabolic networks. The differentially activated PRKCε-RASGRP3-GNB2 network, which interacts with the disorganized DLG2 hub, was additionally found to be differentially expressed among in vitro models of human OS metastasis. PRKCε transcript was more abundant in some metastatic OS tumours; however the difference was not significant overall. In functional studies, PRKCε was not found to be involved in migration of M132 OS cells, but its protein expression was induced in M112 OS cells following IGF-1 stimulation.