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Non-muscle invasive bladder cancer tissues have increased base excision repair capacity
The molecular mechanisms underlying the development and progression of bladder cancer (BC) are complex and have not been fully elucidated. Alterations in base excision repair (BER) capacity, one of several DNA repair mechanisms assigned to preserving genome integrity, have been reported to influence...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7529820/ https://www.ncbi.nlm.nih.gov/pubmed/33004944 http://dx.doi.org/10.1038/s41598-020-73370-z |
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author | Somuncu, Berna Keskin, Selcuk Antmen, Fatma Merve Saglican, Yesim Ekmekcioglu, Aysegul Ertuzun, Tugce Tuna, Mustafa Bilal Obek, Can Wilson, David M. Ince, Umit Kural, Ali Riza Muftuoglu, Meltem |
author_facet | Somuncu, Berna Keskin, Selcuk Antmen, Fatma Merve Saglican, Yesim Ekmekcioglu, Aysegul Ertuzun, Tugce Tuna, Mustafa Bilal Obek, Can Wilson, David M. Ince, Umit Kural, Ali Riza Muftuoglu, Meltem |
author_sort | Somuncu, Berna |
collection | PubMed |
description | The molecular mechanisms underlying the development and progression of bladder cancer (BC) are complex and have not been fully elucidated. Alterations in base excision repair (BER) capacity, one of several DNA repair mechanisms assigned to preserving genome integrity, have been reported to influence cancer susceptibility, recurrence, and progression, as well as responses to chemotherapy and radiotherapy. We report herein that non-muscle invasive BC (NMIBC) tissues exhibit increased uracil incision, abasic endonuclease and gap-filling activities, as well as total BER capacity in comparison to normal bladder tissue from the same patient (p < 0.05). No significant difference was detected in 8-oxoG incision activity between cancer and normal tissues. NMIBC tissues have elevated protein levels of uracil DNA glycosylase, 8-oxoguanine DNA glycosylase, AP endonuclease 1 and DNA polymerase β protein. Moreover, the fold increase in total BER and the individual BER enzyme activities were greater in high-grade tissues than in low-grade NMIBC tissues. These findings suggest that enhanced BER activity may play a role in the etiology of NMIBC and that BER proteins could serve as biomarkers in disease prognosis, progression or response to genotoxic therapeutics, such as Bacillus Calmette–Guérin. |
format | Online Article Text |
id | pubmed-7529820 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-75298202020-10-02 Non-muscle invasive bladder cancer tissues have increased base excision repair capacity Somuncu, Berna Keskin, Selcuk Antmen, Fatma Merve Saglican, Yesim Ekmekcioglu, Aysegul Ertuzun, Tugce Tuna, Mustafa Bilal Obek, Can Wilson, David M. Ince, Umit Kural, Ali Riza Muftuoglu, Meltem Sci Rep Article The molecular mechanisms underlying the development and progression of bladder cancer (BC) are complex and have not been fully elucidated. Alterations in base excision repair (BER) capacity, one of several DNA repair mechanisms assigned to preserving genome integrity, have been reported to influence cancer susceptibility, recurrence, and progression, as well as responses to chemotherapy and radiotherapy. We report herein that non-muscle invasive BC (NMIBC) tissues exhibit increased uracil incision, abasic endonuclease and gap-filling activities, as well as total BER capacity in comparison to normal bladder tissue from the same patient (p < 0.05). No significant difference was detected in 8-oxoG incision activity between cancer and normal tissues. NMIBC tissues have elevated protein levels of uracil DNA glycosylase, 8-oxoguanine DNA glycosylase, AP endonuclease 1 and DNA polymerase β protein. Moreover, the fold increase in total BER and the individual BER enzyme activities were greater in high-grade tissues than in low-grade NMIBC tissues. These findings suggest that enhanced BER activity may play a role in the etiology of NMIBC and that BER proteins could serve as biomarkers in disease prognosis, progression or response to genotoxic therapeutics, such as Bacillus Calmette–Guérin. Nature Publishing Group UK 2020-10-01 /pmc/articles/PMC7529820/ /pubmed/33004944 http://dx.doi.org/10.1038/s41598-020-73370-z Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Somuncu, Berna Keskin, Selcuk Antmen, Fatma Merve Saglican, Yesim Ekmekcioglu, Aysegul Ertuzun, Tugce Tuna, Mustafa Bilal Obek, Can Wilson, David M. Ince, Umit Kural, Ali Riza Muftuoglu, Meltem Non-muscle invasive bladder cancer tissues have increased base excision repair capacity |
title | Non-muscle invasive bladder cancer tissues have increased base excision repair capacity |
title_full | Non-muscle invasive bladder cancer tissues have increased base excision repair capacity |
title_fullStr | Non-muscle invasive bladder cancer tissues have increased base excision repair capacity |
title_full_unstemmed | Non-muscle invasive bladder cancer tissues have increased base excision repair capacity |
title_short | Non-muscle invasive bladder cancer tissues have increased base excision repair capacity |
title_sort | non-muscle invasive bladder cancer tissues have increased base excision repair capacity |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7529820/ https://www.ncbi.nlm.nih.gov/pubmed/33004944 http://dx.doi.org/10.1038/s41598-020-73370-z |
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