PARP-1 Expression is Increased in Colon Adenoma and Carcinoma and Correlates with OGG1

The ethiology of colon cancer is largely dependent on inflammation driven oxidative stress. The analysis of 8-oxodeoxyguanosine (8-oxodGuo) level in leukocyte DNA of healthy controls (138 individuals), patients with benign adenomas (AD, 137 individuals) and with malignant carcinomas (CRC, 169 indivi...

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Main Authors:	Dziaman, Tomasz, Ludwiczak, Hubert, Ciesla, Jaroslaw M., Banaszkiewicz, Zbigniew, Winczura, Alicja, Chmielarczyk, Mateusz, Wisniewska, Ewa, Marszalek, Andrzej, Tudek, Barbara, Olinski, Ryszard
Format:	Online
Language:	English
Published:	Public Library of Science 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4272268/

id	pubmed-4272268
recordtype	oai_dc
spelling	pubmed-42722682014-12-26 PARP-1 Expression is Increased in Colon Adenoma and Carcinoma and Correlates with OGG1 Dziaman, Tomasz Ludwiczak, Hubert Ciesla, Jaroslaw M. Banaszkiewicz, Zbigniew Winczura, Alicja Chmielarczyk, Mateusz Wisniewska, Ewa Marszalek, Andrzej Tudek, Barbara Olinski, Ryszard Research Article The ethiology of colon cancer is largely dependent on inflammation driven oxidative stress. The analysis of 8-oxodeoxyguanosine (8-oxodGuo) level in leukocyte DNA of healthy controls (138 individuals), patients with benign adenomas (AD, 137 individuals) and with malignant carcinomas (CRC, 169 individuals) revealed a significant increase in the level of 8-oxodGuo in leukocyte DNA of AD and CRC patients in comparison to controls. The counteracting mechanism is base excision repair, in which OGG1 and PARP-1 play a key role. We investigated the level of PARP-1 and OGG1 mRNA and protein in diseased and marginal, normal tissues taken from AD and CRC patients and in leukocytes taken from the patients as well as from healthy subjects. In colon tumors the PARP-1 mRNA level was higher than in unaffected colon tissue and in polyp tissues. A high positive correlation was found between PARP-1 and OGG1 mRNA levels in all investigated tissues. This suggests reciprocal influence of PARP-1 and OGG1 on their expression and stability, and may contribute to progression of colon cancer. PARP-1 and OGG1 proteins level was several fold higher in polyps and CRC in comparison to normal colon tissues. Individuals bearing the Cys326Cys genotype of OGG1 were characterized by higher PARP-1 protein level in diseased tissues than the Ser326Cys and Ser326Ser genotypes. Aforementioned result may suggest that the diseased cells with polymorphic OGG1 recruit more PARP protein, which is necessary to remove 8-oxodGuo. Thus, patients with decreased activity of OGG1/polymorphism of the OGG1 gene and higher 8-oxodGuo level may be more susceptible to treatment with PARP-1 inhibitors. Public Library of Science 2014-12-19 /pmc/articles/PMC4272268/ /pubmed/25526641 http://dx.doi.org/10.1371/journal.pone.0115558 Text en © 2014 Dziaman et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Dziaman, Tomasz Ludwiczak, Hubert Ciesla, Jaroslaw M. Banaszkiewicz, Zbigniew Winczura, Alicja Chmielarczyk, Mateusz Wisniewska, Ewa Marszalek, Andrzej Tudek, Barbara Olinski, Ryszard
spellingShingle	Dziaman, Tomasz Ludwiczak, Hubert Ciesla, Jaroslaw M. Banaszkiewicz, Zbigniew Winczura, Alicja Chmielarczyk, Mateusz Wisniewska, Ewa Marszalek, Andrzej Tudek, Barbara Olinski, Ryszard PARP-1 Expression is Increased in Colon Adenoma and Carcinoma and Correlates with OGG1
author_facet	Dziaman, Tomasz Ludwiczak, Hubert Ciesla, Jaroslaw M. Banaszkiewicz, Zbigniew Winczura, Alicja Chmielarczyk, Mateusz Wisniewska, Ewa Marszalek, Andrzej Tudek, Barbara Olinski, Ryszard
author_sort	Dziaman, Tomasz
title	PARP-1 Expression is Increased in Colon Adenoma and Carcinoma and Correlates with OGG1
title_short	PARP-1 Expression is Increased in Colon Adenoma and Carcinoma and Correlates with OGG1
title_full	PARP-1 Expression is Increased in Colon Adenoma and Carcinoma and Correlates with OGG1
title_fullStr	PARP-1 Expression is Increased in Colon Adenoma and Carcinoma and Correlates with OGG1
title_full_unstemmed	PARP-1 Expression is Increased in Colon Adenoma and Carcinoma and Correlates with OGG1
title_sort	parp-1 expression is increased in colon adenoma and carcinoma and correlates with ogg1
description	The ethiology of colon cancer is largely dependent on inflammation driven oxidative stress. The analysis of 8-oxodeoxyguanosine (8-oxodGuo) level in leukocyte DNA of healthy controls (138 individuals), patients with benign adenomas (AD, 137 individuals) and with malignant carcinomas (CRC, 169 individuals) revealed a significant increase in the level of 8-oxodGuo in leukocyte DNA of AD and CRC patients in comparison to controls. The counteracting mechanism is base excision repair, in which OGG1 and PARP-1 play a key role. We investigated the level of PARP-1 and OGG1 mRNA and protein in diseased and marginal, normal tissues taken from AD and CRC patients and in leukocytes taken from the patients as well as from healthy subjects. In colon tumors the PARP-1 mRNA level was higher than in unaffected colon tissue and in polyp tissues. A high positive correlation was found between PARP-1 and OGG1 mRNA levels in all investigated tissues. This suggests reciprocal influence of PARP-1 and OGG1 on their expression and stability, and may contribute to progression of colon cancer. PARP-1 and OGG1 proteins level was several fold higher in polyps and CRC in comparison to normal colon tissues. Individuals bearing the Cys326Cys genotype of OGG1 were characterized by higher PARP-1 protein level in diseased tissues than the Ser326Cys and Ser326Ser genotypes. Aforementioned result may suggest that the diseased cells with polymorphic OGG1 recruit more PARP protein, which is necessary to remove 8-oxodGuo. Thus, patients with decreased activity of OGG1/polymorphism of the OGG1 gene and higher 8-oxodGuo level may be more susceptible to treatment with PARP-1 inhibitors.
publisher	Public Library of Science
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4272268/
_version_	1613169268904427520

PARP-1 Expression is Increased in Colon Adenoma and Carcinoma and Correlates with OGG1

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