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Osteosarcoma (OS) progression is associated with increased nuclear levels and transcriptional activity of Active-β-catenin (ABC)

  • Author / Creator
    Ali, Noureen
  • Osteosarcoma (OS) is an aggressive primary bone malignancy having peak incidence in children and young adults <25 years of age. Outcome remains poor for most patients with metastatic disease which develops in 1 of every 5 cases. However, despite the use of multimodal chemotherapeutic and surgical treatments, survival rates have remained relatively constant over the past two decades. Presently, there is no reliable marker available for predicting invasive/metastatic disease. This highlights the need to understand the underlying biology of OS to design improved therapeutic interventions and identify prognostic and/or predictive markers which will facilitate stratification of patients to administer treatment options relevant to each patient group, thus allowing for better management of OS. The canonical Wnt/β-catenin pathway is important for a number of cellular processes and is also known to be a critical pathway in OS development and progression. Thus, we investigate Wnt/β-catenin signaling, specifically, the roles of its effector molecules β-catenin and the transcriptionally active form of β-catenin, Activated-β-Catenin (ABC), in OS progression. We used an in vitro model comprising of two pairs of OS cell lines that model OS progression. Our results show significantly upregulated nuclear ABC levels and increased activity of ABC, but not β-catenin, in metastatic OS cell lines compared to parental ones. Furthermore, our immunohistochemical studies showed presence of positive nuclear ABC staining in 85% of the OS tissue cores tested and a significant association between nuclear ABC staining and age. Hence, our findings propose ABC as a prognostic marker for survival in OS.

  • Subjects / Keywords
  • Graduation date
    Spring 2019
  • Type of Item
    Thesis
  • Degree
    Master of Science
  • DOI
    https://doi.org/10.7939/r3-fee6-1n46
  • License
    Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.