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Protein Kinase C Epsilon and Genetic Networks in Osteosarcoma Metastasis
Department of Molecular Genetics, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Ave., Toronto, ON M5G 1X5, Canada
The Centre for Applied Genomics, The Hospital for Sick Children, MaRS Centre—East Tower, 101 College Street Rm.14-701, Toronto, ON M5G 1L7, Canada
* Author to whom correspondence should be addressed.
Received: 16 February 2013; in revised form: 22 March 2013 / Accepted: 26 March 2013 / Published: 8 April 2013
Abstract: Osteosarcoma (OS) is the most common primary malignant tumor of the bone, and pulmonary metastasis is the most frequent cause of OS mortality. The aim of this study was to discover and characterize genetic networks differentially expressed in metastatic OS. Expression profiling of OS tumors, and subsequent supervised network analysis, was performed to discover genetic networks differentially activated or organized in metastatic OS compared to localized OS. Broad trends among the profiles of metastatic tumors include 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 also found to be differentially expressed among OS cell lines with differing metastatic capacity in xenograft models. PRKCε transcript was more abundant in some metastatic OS tumors; 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.
Keywords: osteosarcoma; metastasis; expression profiling; network analysis; Dynemo; protein kinase C epsilon
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MDPI and ACS Style
Goudarzi, A.; Gokgoz, N.; Gill, M.; Pinnaduwage, D.; Merico, D.; Wunder, J.S.; Andrulis, I.L. Protein Kinase C Epsilon and Genetic Networks in Osteosarcoma Metastasis. Cancers 2013, 5, 372-403.
Goudarzi A, Gokgoz N, Gill M, Pinnaduwage D, Merico D, Wunder JS, Andrulis IL. Protein Kinase C Epsilon and Genetic Networks in Osteosarcoma Metastasis. Cancers. 2013; 5(2):372-403.
Goudarzi, Atta; Gokgoz, Nalan; Gill, Mona; Pinnaduwage, Dushanthi; Merico, Daniele; Wunder, Jay S.; Andrulis, Irene L. 2013. "Protein Kinase C Epsilon and Genetic Networks in Osteosarcoma Metastasis." Cancers 5, no. 2: 372-403.