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GPX2 promotes development of bladder cancer with squamous cell differentiation through the control of apoptosis

Herein, we elucidated the molecular mechanisms and therapeutic potential of glutathione peroxidase 2 (GPX2) in bladder cancer. GPX2 expression gradually increased during progression from normal to papillary or nodular hyperplasia (PNHP) and urothelial carcinoma (UC) in a rat N-butyl-N-(4-hydroxybuty...

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Autores principales: Naiki, Taku, Naiki-Ito, Aya, Iida, Keitaro, Etani, Toshiki, Kato, Hiroyuki, Suzuki, Shugo, Yamashita, Yoriko, Kawai, Noriyasu, Yasui, Takahiro, Takahashi, Satoru
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5882302/
https://www.ncbi.nlm.nih.gov/pubmed/29662611
http://dx.doi.org/10.18632/oncotarget.24627
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author Naiki, Taku
Naiki-Ito, Aya
Iida, Keitaro
Etani, Toshiki
Kato, Hiroyuki
Suzuki, Shugo
Yamashita, Yoriko
Kawai, Noriyasu
Yasui, Takahiro
Takahashi, Satoru
author_facet Naiki, Taku
Naiki-Ito, Aya
Iida, Keitaro
Etani, Toshiki
Kato, Hiroyuki
Suzuki, Shugo
Yamashita, Yoriko
Kawai, Noriyasu
Yasui, Takahiro
Takahashi, Satoru
author_sort Naiki, Taku
collection PubMed
description Herein, we elucidated the molecular mechanisms and therapeutic potential of glutathione peroxidase 2 (GPX2) in bladder cancer. GPX2 expression gradually increased during progression from normal to papillary or nodular hyperplasia (PNHP) and urothelial carcinoma (UC) in a rat N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced bladder carcinogenesis model. GPX2 overexpression was more marked in UC with squamous differentiation (SqD) than in pure UC. Clinical intraepithelial lesions of papillary UC and invasive UC with SqD also had strong GPX2 expression in human radical cystectomy specimens. In addition, prognostic analysis using transurethral specimens revealed that low expression level of GPX2 predicted poor prognosis in patients with pure UC. Further, UC cell lines, BC31 and RT4, cultured in vitro also overexpressed GPX2. Knock-down of GPX2 induced significant inhibition of intracellular reactive oxygen species (ROS) production, in addition to significant growth inhibition and increased apoptosis with activation of caspase 3 or 7 in both BC31 and RT4 cells. Interestingly, tumor growth of BC31 cells subcutaneously transplanted in nude mice was significantly caused the induction of apoptosis, as well as inhibition of angiogenesis and SqD by GPX2 down-regulation. Our findings demonstrated that GPX2 plays an important role in bladder carcinogenesis through the regulation of apoptosis against intracellular ROS, and may be considered as a novel biomarker or therapeutic target in bladder cancer.
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spelling pubmed-58823022018-04-16 GPX2 promotes development of bladder cancer with squamous cell differentiation through the control of apoptosis Naiki, Taku Naiki-Ito, Aya Iida, Keitaro Etani, Toshiki Kato, Hiroyuki Suzuki, Shugo Yamashita, Yoriko Kawai, Noriyasu Yasui, Takahiro Takahashi, Satoru Oncotarget Research Paper Herein, we elucidated the molecular mechanisms and therapeutic potential of glutathione peroxidase 2 (GPX2) in bladder cancer. GPX2 expression gradually increased during progression from normal to papillary or nodular hyperplasia (PNHP) and urothelial carcinoma (UC) in a rat N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced bladder carcinogenesis model. GPX2 overexpression was more marked in UC with squamous differentiation (SqD) than in pure UC. Clinical intraepithelial lesions of papillary UC and invasive UC with SqD also had strong GPX2 expression in human radical cystectomy specimens. In addition, prognostic analysis using transurethral specimens revealed that low expression level of GPX2 predicted poor prognosis in patients with pure UC. Further, UC cell lines, BC31 and RT4, cultured in vitro also overexpressed GPX2. Knock-down of GPX2 induced significant inhibition of intracellular reactive oxygen species (ROS) production, in addition to significant growth inhibition and increased apoptosis with activation of caspase 3 or 7 in both BC31 and RT4 cells. Interestingly, tumor growth of BC31 cells subcutaneously transplanted in nude mice was significantly caused the induction of apoptosis, as well as inhibition of angiogenesis and SqD by GPX2 down-regulation. Our findings demonstrated that GPX2 plays an important role in bladder carcinogenesis through the regulation of apoptosis against intracellular ROS, and may be considered as a novel biomarker or therapeutic target in bladder cancer. Impact Journals LLC 2018-03-23 /pmc/articles/PMC5882302/ /pubmed/29662611 http://dx.doi.org/10.18632/oncotarget.24627 Text en Copyright: © 2018 Naiki et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (http://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Naiki, Taku
Naiki-Ito, Aya
Iida, Keitaro
Etani, Toshiki
Kato, Hiroyuki
Suzuki, Shugo
Yamashita, Yoriko
Kawai, Noriyasu
Yasui, Takahiro
Takahashi, Satoru
GPX2 promotes development of bladder cancer with squamous cell differentiation through the control of apoptosis
title GPX2 promotes development of bladder cancer with squamous cell differentiation through the control of apoptosis
title_full GPX2 promotes development of bladder cancer with squamous cell differentiation through the control of apoptosis
title_fullStr GPX2 promotes development of bladder cancer with squamous cell differentiation through the control of apoptosis
title_full_unstemmed GPX2 promotes development of bladder cancer with squamous cell differentiation through the control of apoptosis
title_short GPX2 promotes development of bladder cancer with squamous cell differentiation through the control of apoptosis
title_sort gpx2 promotes development of bladder cancer with squamous cell differentiation through the control of apoptosis
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5882302/
https://www.ncbi.nlm.nih.gov/pubmed/29662611
http://dx.doi.org/10.18632/oncotarget.24627
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