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

Abstract

// Tao Wang 1,2 , Zhuo Liu 1,2 , Shuiming Guo 1,2 , Licheng Wu 1,2 , Mingchao Li 1,2 , Jun Yang 1,2 , Ruibao Chen 1,2 , Hua Xu 1,2 , Shaoxin Cai 3 , Hui Chen 5 , Weiyong Li 5 , Liang Wang 4 , Zhiquan Hu 1,2 , Qianyuan Zhuang 1,2 , Shaohua Xu 6 , Liping Wang 6 , Jihong Liu 1,2 , Zhangqun Ye 1,2 , Jun-Yuan Ji 7 , Chenguang Wang 6 , Ke Chen 1,2 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 G 0 /G 1 phases, and induced apoptotic cell death accompanied by down-regulation of IGF-1, ErbB2, and VEGF downstream kinases PI 3 K/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.