title: The tumor suppressive role of CAMK2N1 in castration-resistant prostate cancer.
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.
authors.affiliation: Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, China; Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Liu
authors.forename: Shuiming
authors.initials: S
authors.lastname: Guo
authors.forename: Licheng
authors.initials: L
authors.lastname: Wu
authors.forename: Mingchao
authors.initials: M
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.forename: Ruibao
authors.initials: R
authors.lastname: Chen
authors.forename: Hua
authors.initials: H
authors.lastname: Xu
authors.forename: Shaoxin
authors.initials: S
authors.lastname: Cai
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.forename: Weiyong
authors.initials: W
authors.lastname: Li
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.forename: Zhiquan
authors.initials: Z
authors.lastname: Hu
authors.forename: Qianyuan
authors.initials: Q
authors.lastname: Zhuang
authors.forename: Shaohua
authors.initials: S
authors.lastname: Xu
authors.forename: Liping
authors.initials: L
authors.lastname: Wang
authors.forename: Jihong
authors.initials: J
authors.lastname: Liu
authors.forename: Zhangqun
authors.initials: Z
authors.lastname: Ye
authors.forename: Jun-Yuan
authors.initials: JY
authors.lastname: Ji
authors.forename: Chenguang
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, China; Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D018450:Disease Progression; D016147:Genes, Tumor Suppressor; D064593:Heterografts; D006801:Humans; D008297:Male; D008819:Mice, Nude; D064129:Prostatic Neoplasms, Castration-Resistant / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D011506:Proteins / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C529569:CAMK2N1 protein, human; D011506:Proteins; D012333:RNA, Messenger