Oncotarget

Research Papers:

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

Tao Wang, Zhuo Liu, Shuiming Guo, Licheng Wu, Mingchao Li, Jun Yang, Ruibao Chen, Hua Xu, Shaoxin Cai, Hui Chen, Weiyong Li, Liang Wang, Zhiquan Hu, Qianyuan Zhuang, Shaohua Xu, Liping Wang, Jihong Liu, Zhangqun Ye, Jun-Yuan Ji, Chenguang Wang and Ke Chen _

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Oncotarget. 2014; 5:3611-3621. https://doi.org/10.18632/oncotarget.1968

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Abstract

Tao Wang1,2, Zhuo Liu1,2, Shuiming Guo1,2, Licheng Wu1,2, Mingchao Li1,2, Jun Yang1,2, Ruibao Chen1,2, Hua Xu1,2, Shaoxin Cai3, Hui Chen5, Weiyong Li5, Liang Wang4, Zhiquan Hu1,2, Qianyuan Zhuang1,2, Shaohua Xu6, Liping Wang6, Jihong Liu1,2, Zhangqun Ye1,2, Jun-Yuan Ji7, Chenguang Wang6, Ke Chen1,2

1 Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, China

2 Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, China

3 Department of Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, China

4 Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, China

5 Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, China

6 Kimmel Cancer Center, Department of Cancer Biology, Thomas Jefferson University, Philadelphia, PA, USA

7 Department of Molecular and Cellular Medicine, College of Medicine, Texas A&M University Health Science Center, College Station, TX 77843, USA.

Correspondence:

Ke Chen, email:

Keywords: CAMK2N1, prostate cancer, tumor suppressor

Received: March 25, 2014 Accepted: May 12, 2014 Published: May 13, 2014

Abstract

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.


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