The tumor suppressive role of CAMK2N1 in castration-resistant prostate cancer

Prostate cancer at advanced stages including metastatic and castration-resistant cancer remains incurable due to the lack of effective therapies. The CAMK2N1 gene, cloned and characterized as an inhibitor of CaMKII (calcium/calmodulin-dependent protein kinase II), has been shown to affect tumorigene...

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Main Authors: Wang, Tao, Liu, Zhuo, Guo, Shuiming, Wu, Licheng, Li, Mingchao, Yang, Jun, Chen, Ruibao, Xu, Hua, Cai, Shaoxin, Chen, Hui, Li, Weiyong, Wang, Liang, Hu, Zhiquan, Zhuang, Qianyuan, Xu, Shaohua, Wang, Liping, Liu, Jihong, Ye, Zhangqun, Ji, Jun-Yuan, Wang, Chenguang, Chen, Ke
Format: Online
Language:English
Published: Impact Journals LLC 2014
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4116507/
id pubmed-4116507
recordtype oai_dc
spelling pubmed-41165072014-08-04 The tumor suppressive role of CAMK2N1 in castration-resistant prostate cancer Wang, Tao Liu, Zhuo Guo, Shuiming Wu, Licheng Li, Mingchao Yang, Jun Chen, Ruibao Xu, Hua Cai, Shaoxin Chen, Hui Li, Weiyong Wang, Liang Hu, Zhiquan Zhuang, Qianyuan Xu, Shaohua Wang, Liping Liu, Jihong Ye, Zhangqun Ji, Jun-Yuan Wang, Chenguang Chen, Ke Research Paper Prostate cancer at advanced stages including metastatic and castration-resistant cancer remains incurable due to the lack of effective therapies. The CAMK2N1 gene, cloned and characterized as an inhibitor of CaMKII (calcium/calmodulin-dependent protein kinase II), has been shown to affect tumorigenesis and tumor growth. However, it is still unknown whether CAMK2N1 plays a role in prostate cancer development. We first examined the protein and mRNA levels of CAMK2N1 and observed a significant decrease in human prostate cancers comparing to normal prostate tissues. Re-expression of CAMK2N1 in prostate cancer cells reduced cellular proliferation, arrested cells in G0/G1 phases, and induced apoptotic cell death accompanied by down-regulation of IGF-1, ErbB2, and VEGF downstream kinases PI3K/AKT, as well as the MEK/ERK-mediated signaling pathways. Conversely, knockdown of CAMK2N1 had a significant opposite effects on these phenotypes. Our analyses suggest that CAMK2N1 plays a tumor suppressive role in prostate cancer cells. Reduced CAMK2N1 expression correlates to human prostate cancer progression and predicts poor clinical outcome, indicating that CAMK2N1 may serve as a biomarker. The inhibition of tumor growth by expressing CAMK2N1 established a role of CAMK2N1 as a therapeutic target. Impact Journals LLC 2014-05-13 /pmc/articles/PMC4116507/ /pubmed/25003983 Text en Copyright: © 2014 Wang et al. http://creativecommons.org/licenses/by/2.5/ 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 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 Wang, Tao
Liu, Zhuo
Guo, Shuiming
Wu, Licheng
Li, Mingchao
Yang, Jun
Chen, Ruibao
Xu, Hua
Cai, Shaoxin
Chen, Hui
Li, Weiyong
Wang, Liang
Hu, Zhiquan
Zhuang, Qianyuan
Xu, Shaohua
Wang, Liping
Liu, Jihong
Ye, Zhangqun
Ji, Jun-Yuan
Wang, Chenguang
Chen, Ke
spellingShingle Wang, Tao
Liu, Zhuo
Guo, Shuiming
Wu, Licheng
Li, Mingchao
Yang, Jun
Chen, Ruibao
Xu, Hua
Cai, Shaoxin
Chen, Hui
Li, Weiyong
Wang, Liang
Hu, Zhiquan
Zhuang, Qianyuan
Xu, Shaohua
Wang, Liping
Liu, Jihong
Ye, Zhangqun
Ji, Jun-Yuan
Wang, Chenguang
Chen, Ke
The tumor suppressive role of CAMK2N1 in castration-resistant prostate cancer
author_facet Wang, Tao
Liu, Zhuo
Guo, Shuiming
Wu, Licheng
Li, Mingchao
Yang, Jun
Chen, Ruibao
Xu, Hua
Cai, Shaoxin
Chen, Hui
Li, Weiyong
Wang, Liang
Hu, Zhiquan
Zhuang, Qianyuan
Xu, Shaohua
Wang, Liping
Liu, Jihong
Ye, Zhangqun
Ji, Jun-Yuan
Wang, Chenguang
Chen, Ke
author_sort Wang, Tao
title The tumor suppressive role of CAMK2N1 in castration-resistant prostate cancer
title_short The tumor suppressive role of CAMK2N1 in castration-resistant prostate cancer
title_full The tumor suppressive role of CAMK2N1 in castration-resistant prostate cancer
title_fullStr The tumor suppressive role of CAMK2N1 in castration-resistant prostate cancer
title_full_unstemmed The tumor suppressive role of CAMK2N1 in castration-resistant prostate cancer
title_sort tumor suppressive role of camk2n1 in castration-resistant prostate cancer
description Prostate cancer at advanced stages including metastatic and castration-resistant cancer remains incurable due to the lack of effective therapies. The CAMK2N1 gene, cloned and characterized as an inhibitor of CaMKII (calcium/calmodulin-dependent protein kinase II), has been shown to affect tumorigenesis and tumor growth. However, it is still unknown whether CAMK2N1 plays a role in prostate cancer development. We first examined the protein and mRNA levels of CAMK2N1 and observed a significant decrease in human prostate cancers comparing to normal prostate tissues. Re-expression of CAMK2N1 in prostate cancer cells reduced cellular proliferation, arrested cells in G0/G1 phases, and induced apoptotic cell death accompanied by down-regulation of IGF-1, ErbB2, and VEGF downstream kinases PI3K/AKT, as well as the MEK/ERK-mediated signaling pathways. Conversely, knockdown of CAMK2N1 had a significant opposite effects on these phenotypes. Our analyses suggest that CAMK2N1 plays a tumor suppressive role in prostate cancer cells. Reduced CAMK2N1 expression correlates to human prostate cancer progression and predicts poor clinical outcome, indicating that CAMK2N1 may serve as a biomarker. The inhibition of tumor growth by expressing CAMK2N1 established a role of CAMK2N1 as a therapeutic target.
publisher Impact Journals LLC
publishDate 2014
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4116507/
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