The tumor suppressive role of CAMK2N1 in castration-resistant prostate cancer Academic Article uri icon

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.

author list (cited authors)

  • Wang, T., Liu, Z., Guo, S., Wu, L., Li, M., Yang, J., ... Chen, K. e.

complete list of 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