title: CAMK2N1 inhibits prostate cancer progression through androgen receptor-dependent signaling.
abstract: Castration resistance is a major obstacle to hormonal therapy for prostate cancer patients. Although androgen independence of prostate cancer growth is a known contributing factor to endocrine resistance, the mechanism of androgen receptor deregulation in endocrine resistance is still poorly understood. Herein, the CAMK2N1 was shown to contribute to the human prostate cancer cell growth and survival through AR-dependent signaling. Reduced expression of CAMK2N1 was correlated to recurrence-free survival of prostate cancer patients with high levels of AR expression in their tumor. CAMK2N1 and AR signaling form an auto-regulatory negative feedback loop: CAMK2N1 expression was down-regulated by AR activation; while CAMK2N1 inhibited AR expression and transactivation through CAMKII and AKT pathways. Knockdown of CAMK2N1 in prostate cancer cells alleviated Casodex inhibition of cell growth, while re-expression of CAMK2N1 in castration-resistant cells sensitized the cells to Casodex treatment. Taken together, our findings suggest that CAMK2N1 plays a tumor suppressive role and serves as a crucial determinant of the resistance of prostate cancer to endocrine therapies.
authors.affiliation: Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Shuiming
authors.initials: S
authors.lastname: Guo
authors.affiliation: Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Licheng
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Mingchao
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Ruibao
authors.initials: R
authors.lastname: Chen
authors.affiliation: Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Xiaming
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Shaoxin
authors.initials: S
authors.lastname: Cai
authors.affiliation: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.affiliation: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Weiyong
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Gynecology, Shanghai First Matenity and Infant Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Shaohua
authors.initials: S
authors.lastname: Xu
authors.affiliation: Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Zhiquan
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Qianyuan
authors.initials: Q
authors.lastname: Zhuang
authors.affiliation: Kimmel Cancer Center, Department of Cancer Biology, Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: Liping
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Kongming
authors.initials: K
authors.lastname: Wu
authors.affiliation: Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Jihong
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Zhangqun
authors.initials: Z
authors.lastname: Ye
authors.affiliation: Department of Molecular and Cellular Medicine, College of Medicine, Texas A&M University Health Science Center, College Station, TX, USA.
authors.forename: Jun-Yuan
authors.initials: JY
authors.lastname: Ji
authors.affiliation: Key Laboratory of Tianjin Radiation and Molecular Nuclear Medicine; Institute of Radiation Medicine, Peking Union Medical College & Chinese Academy of Medical Sciences, Tianjin, China.
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, Wuhan, Hubei, China. Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Chen
mesh_terms: D000726:Androgen Antagonists / Q000494:pharmacology; D000813:Anilides / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D063646:Carcinogenesis / Q000235:genetics; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D048708:Cell Growth Processes / Q000235:genetics; D004351:Drug Resistance / Q000235:genetics; D025461:Feedback, Physiological; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D008297:Male; D009570:Nitriles / Q000494:pharmacology; D051058:Oncogene Protein v-akt / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D011944:Receptors, Androgen / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D016019:Survival Analysis; D014105:Tosyl Compounds / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D000726:Androgen Antagonists; D000813:Anilides; D000970:Antineoplastic Agents; C529569:CAMK2N1 protein, human; D009570:Nitriles; D011506:Proteins; D034741:RNA, Small Interfering; D011944:Receptors, Androgen; D014105:Tosyl Compounds; C053541:bicalutamide; D051058:Oncogene Protein v-akt; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2