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Journal of Experimental & Clinical Cancer Research
Published in: Journal of Experimental & Clinical Cancer Research 1/2017

Open Access 01-12-2017 | Research

Angiotensin II type 2 receptor promotes apoptosis and inhibits angiogenesis in bladder cancer

Authors: Nana Pei, Yingying Mao, Pengfei Wan, Xinglu Chen, Andrew Li, Huiying Chen, Jinlong Li, Renqiang Wan, Yanling Zhang, Hongyan Du, Baihong Chen, Guangyu Jiang, Minghan Xia, Colin Sumners, Guixue Hu, Dongsheng Gu, Hongwei Li

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2017

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Abstract

Background

Bladder cancer (BCa) is the ninth most common form of cancer in the world. There is a continuing need not only for improving the accuracy of diagnostic markers but also for the development of new treatment strategies. Recent studies have shown that the renin-angiotensin system (RAS), which include the angiotensin type 1 (AT1R), type 2(AT2R), and Mas receptors, play an important role in tumorigenesis and may guide us in meeting those needs.

Results

In this study, we first observed that AT1R and Mas expression levels were significantly upregulated in BCa specimens while AT2R was significantly downregulated. Viral vector mediated overexpression of AT2R induced apoptosis and dramatically suppressed BCa cell proliferation in vitro, suggesting a therapeutic effect. Investigation into the mechanism revealed that the overexpression of AT2R increases the expression levels of caspase-3, caspase-8, and p38 and decreases the expression level of pErk. AT2R overexpression also leads to upregulation of 2 apoptosis-related genes (BCL2A1, TNFSF25) and downregulation of 8 apoptosis-related genes (CASP 6, CASP 9, DFFA, IGF1R, PYCARD, TNF, TNFRSF21, TNFSF10, NAIP) in transduced EJ cells as determined by PCR Array analysis. In vivo, we observed that AT2R overexpression caused significant reduction in xenograft tumors sizes by downregulation VEGF and induction of apoptosis.

Conclusions

Taken together, the data suggest that AT1R, AT2R or Mas could be used as a diagnostic marker of BCa and AT2R is a promising novel target gene for BCa gene therapy.
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Metadata
Title
Angiotensin II type 2 receptor promotes apoptosis and inhibits angiogenesis in bladder cancer
Authors
Nana Pei
Yingying Mao
Pengfei Wan
Xinglu Chen
Andrew Li
Huiying Chen
Jinlong Li
Renqiang Wan
Yanling Zhang
Hongyan Du
Baihong Chen
Guangyu Jiang
Minghan Xia
Colin Sumners
Guixue Hu
Dongsheng Gu
Hongwei Li
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2017
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/s13046-017-0542-0

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