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Poly (ADP-ribose) polymerase-1 inhibition decreases proliferation through G2/M arrest in esophageal squamous cell carcinoma

Poly (ADP-ribose) polymerase-1 (PARP1) plays a vital role in DNA repair and is expected to be an effective target in various malignancies. The aim of the present study was to investigate the clinical and biological significance of PARP1 expression in esophageal squamous cell carcinoma (ESCC). Immuno...

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Autores principales: Yamamoto, Masaaki, Yamasaki, Makoto, Tsukao, Yukiko, Tanaka, Koji, Miyazaki, Yasuhiro, Makino, Tomoki, Takahashi, Tsuyoshi, Kurokawa, Yukinori, Nakajima, Kiyokazu, Takiguchi, Shuji, Mori, Masaki, Doki, Yuichiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5529935/
https://www.ncbi.nlm.nih.gov/pubmed/28789382
http://dx.doi.org/10.3892/ol.2017.6334
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author Yamamoto, Masaaki
Yamasaki, Makoto
Tsukao, Yukiko
Tanaka, Koji
Miyazaki, Yasuhiro
Makino, Tomoki
Takahashi, Tsuyoshi
Kurokawa, Yukinori
Nakajima, Kiyokazu
Takiguchi, Shuji
Mori, Masaki
Doki, Yuichiro
author_facet Yamamoto, Masaaki
Yamasaki, Makoto
Tsukao, Yukiko
Tanaka, Koji
Miyazaki, Yasuhiro
Makino, Tomoki
Takahashi, Tsuyoshi
Kurokawa, Yukinori
Nakajima, Kiyokazu
Takiguchi, Shuji
Mori, Masaki
Doki, Yuichiro
author_sort Yamamoto, Masaaki
collection PubMed
description Poly (ADP-ribose) polymerase-1 (PARP1) plays a vital role in DNA repair and is expected to be an effective target in various malignancies. The aim of the present study was to investigate the clinical and biological significance of PARP1 expression in esophageal squamous cell carcinoma (ESCC). Immunohistochemical (IHC) staining was used to examine the association between PARP1 expression and the clinicopathological features of 86 patients with ESCC. The antitumor effect of small interfering RNA against PARP1 (siPARP1) was examined in a proliferation assay, and the mechanisms of this effect were investigated using western blot analysis and cell cycle assays. Cox multivariate analysis revealed that high expression of PARP1 in IHC staining was a statistically significant independent prognostic factor of poor overall survival (OS). The adjusted hazard ratio for OS in the group with high expression of PARP1 was 2.39 (95% confidence interval, 1.29–4.44; P=0.0051). In vitro assays showed that siPARP1 significantly decreased proliferation through G2/M arrest. Furthermore, western blot analysis showed that PARP1 was associated with the ataxia telangiectasia mutated-checkpoint kinase 2-cell division control 25c pathway. The present study suggests that PARP1 expression has a critical role in ESCC progression, and may be a clinical therapeutic target.
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spelling pubmed-55299352017-08-07 Poly (ADP-ribose) polymerase-1 inhibition decreases proliferation through G2/M arrest in esophageal squamous cell carcinoma Yamamoto, Masaaki Yamasaki, Makoto Tsukao, Yukiko Tanaka, Koji Miyazaki, Yasuhiro Makino, Tomoki Takahashi, Tsuyoshi Kurokawa, Yukinori Nakajima, Kiyokazu Takiguchi, Shuji Mori, Masaki Doki, Yuichiro Oncol Lett Articles Poly (ADP-ribose) polymerase-1 (PARP1) plays a vital role in DNA repair and is expected to be an effective target in various malignancies. The aim of the present study was to investigate the clinical and biological significance of PARP1 expression in esophageal squamous cell carcinoma (ESCC). Immunohistochemical (IHC) staining was used to examine the association between PARP1 expression and the clinicopathological features of 86 patients with ESCC. The antitumor effect of small interfering RNA against PARP1 (siPARP1) was examined in a proliferation assay, and the mechanisms of this effect were investigated using western blot analysis and cell cycle assays. Cox multivariate analysis revealed that high expression of PARP1 in IHC staining was a statistically significant independent prognostic factor of poor overall survival (OS). The adjusted hazard ratio for OS in the group with high expression of PARP1 was 2.39 (95% confidence interval, 1.29–4.44; P=0.0051). In vitro assays showed that siPARP1 significantly decreased proliferation through G2/M arrest. Furthermore, western blot analysis showed that PARP1 was associated with the ataxia telangiectasia mutated-checkpoint kinase 2-cell division control 25c pathway. The present study suggests that PARP1 expression has a critical role in ESCC progression, and may be a clinical therapeutic target. D.A. Spandidos 2017-08 2017-06-07 /pmc/articles/PMC5529935/ /pubmed/28789382 http://dx.doi.org/10.3892/ol.2017.6334 Text en Copyright: © Yamamoto et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Yamamoto, Masaaki
Yamasaki, Makoto
Tsukao, Yukiko
Tanaka, Koji
Miyazaki, Yasuhiro
Makino, Tomoki
Takahashi, Tsuyoshi
Kurokawa, Yukinori
Nakajima, Kiyokazu
Takiguchi, Shuji
Mori, Masaki
Doki, Yuichiro
Poly (ADP-ribose) polymerase-1 inhibition decreases proliferation through G2/M arrest in esophageal squamous cell carcinoma
title Poly (ADP-ribose) polymerase-1 inhibition decreases proliferation through G2/M arrest in esophageal squamous cell carcinoma
title_full Poly (ADP-ribose) polymerase-1 inhibition decreases proliferation through G2/M arrest in esophageal squamous cell carcinoma
title_fullStr Poly (ADP-ribose) polymerase-1 inhibition decreases proliferation through G2/M arrest in esophageal squamous cell carcinoma
title_full_unstemmed Poly (ADP-ribose) polymerase-1 inhibition decreases proliferation through G2/M arrest in esophageal squamous cell carcinoma
title_short Poly (ADP-ribose) polymerase-1 inhibition decreases proliferation through G2/M arrest in esophageal squamous cell carcinoma
title_sort poly (adp-ribose) polymerase-1 inhibition decreases proliferation through g2/m arrest in esophageal squamous cell carcinoma
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5529935/
https://www.ncbi.nlm.nih.gov/pubmed/28789382
http://dx.doi.org/10.3892/ol.2017.6334
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