De Faveri, LE, Hurst, CD, Roulson, J et al. (4 more authors) (2015) Polycomb repressor complex 1 member, BMI1 contributes to urothelial tumorigenesis through p16-independent mechanisms. Translational Oncology, 8 (5). pp. 387-399. ISSN 1944-7124
Abstract
Urothelial carcinoma (UC) causes significant morbidity and remains the most expensive cancer to treat due to the need for repeated resections and life-long monitoring for patients with non-muscle-invasive bladder cancer (NMIBC). Novel therapeutics and stratification approaches are needed to improve the outlook for both NMIBC and muscle-invasive bladder cancer (MIBC). We investigated the expression and effects of B Lymphoma Mo-MLV Insertion Region 1 (BMI1) in UC. BMI1 was found to be over-expressed in most UC cell lines and primary tumors by quantitative-real-time-PCR and immunohistochemistry. In contrast to some previous reports, no association with tumor stage or grade was observed in 2 independent tumor panels. Furthermore, up-regulation of BMI1 was detected in premalignant bladder lesions, suggesting a role early in tumorigenesis. BMI1 is not located within a common region of genomic amplification in UC. The CDKN2A locus (which encodes the p16 tumor suppressor gene) is a transcriptional target of BMI1 in some cellular contexts. In UC cell lines and primary tissues, no correlation between BMI1 and p16 expression was observed. Retroviral-mediated over-expression of BMI1 immortalized normal human urothelial cells (NHUC) in vitro and was associated with induction of telomerase activity, bypass of senescence and repression of differentiation. The effects of BMI1 on gene expression were identified by expression microarray analysis of NHUC-BMI1. MetacoreTM analysis of the gene expression profile implicated downstream effects of BMI1 on α4/β1 integrin-mediated adhesion, cytoskeleton remodelling and CREB1-mediated transcription.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2015 The Authors. Published by Elsevier Inc. on behalf of Neoplasia Press, Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
Keywords: | bladder; BMI1; urothelial carcinoma; immoratlization; tumorigenesis |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) The University of Leeds > Faculty of Medicine and Health (Leeds) > Institute of Molecular Medicine (LIMM) (Leeds) > Section of Experimental Oncology (Leeds) The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cancer and Pathology (LICAP) > Section of Experimental Oncology (Leeds) The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Inst of Clinical Trials Research (LICTR) (Leeds) |
Funding Information: | Funder Grant number Yorkshire Cancer Research L355 |
Depositing User: | Symplectic Publications |
Date Deposited: | 18 Aug 2015 11:28 |
Last Modified: | 05 Apr 2018 11:39 |
Published Version: | http://dx.doi.org/10.1016/j.tranon.2015.08.002 |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.tranon.2015.08.002 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:89006 |