Alsiary, R, Brownhill, SC, Brüning-Richardson, A orcid.org/0000-0002-9862-9805 et al. (6 more authors) (2018) Expression analysis of the MCPH1/BRIT1 and BRCA1 tumor suppressor genes and telomerase splice variants in epithelial ovarian cancer. Gene, 672. pp. 34-44. ISSN 1879-0038
Abstract
Aims
The aim of this study was to explore the correlation of hTERT splice variant expression with MCPH1/BRIT1 and BRCA1 expression in epithelial ovarian cancer (EOC) samples.
Background
Telomerase activation can contribute to the progression of tumors and the development of cancer. However, the regulation of telomerase activity remains unclear. MCPH1 (also known as BRIT1, BRCT-repeat inhibitor of hTERT expression) and BRCA1 are tumor suppressor genes that have been linked to telomerase expression.
Methods
qPCR was used to investigate telomerase splice variants, MCPH1/BRIT1 and BRCA1 expression in EOC tissue and primary cultures.
Results
The wild type α+/β+ hTERT variant was the most common splice variant in the EOC samples, followed by α+/β− hTERT, a dominant negative regulator of telomerase activity. EOC samples expressing high total hTERT demonstrated significantly lower MCPH1/BRIT1 expression in both tissue (p = 0.05) and primary cultures (p = 0.03). We identified a negative correlation between MCPH1/BRIT1 and α+/β+ hTERT (p = 0.04), and a strong positive association between MCPH1/BRIT1 and both α−/β+ hTERT and α−/β− hTERT (both p = 0.02). A positive association was observed between BRCA1 and α−/β+ hTERT and α−/β− hTERT expression (p = 0.003 and p = 0.04, respectively).
Conclusions
These findings support a regulatory effect of MCPH1/BRIT1 and BRCA1 on telomerase activity, particularly the negative association between MCPH1/BRIT1 and the functional form of hTERT (α+/β+).
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | (c) 2018 Elsevier B.V. All rights reserved. This is an author produced version of a paper published in Gene. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | Telomerase; hTERT; Epithelial ovarian cancer; BRIT1; MCPH1; BRCA1 |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > Institute of Molecular Medicine (LIMM) (Leeds) > Section of Opthalmology and Neurosciences (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 05 Jun 2018 12:26 |
Last Modified: | 31 May 2019 00:41 |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.gene.2018.05.113 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:131684 |