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: Tao Wang, Shuiming Guo, Zhuo Liu, Licheng Wu, Mingchao Li, Jun Yang, Ruibao Chen, Xiaming Liu, Hua Xu, Shaoxin Cai, Hui Chen, Weiyong Li, Shaohua Xu, Liang Wang, Zhiquan Hu, Qianyuan Zhuang, Liping Wang, Kongming Wu, Jihong Liu, Zhangqun Ye, Jun-Yuan Ji, Chenguang Wang, Ke Chen
• Journal: Oncotarget (Oncotarget) Vol. 5 Issue 21 Pg. 10293-306 (Nov 15 2014) ISSN: 1949-2553 [Electronic] United States
• PMID: 25296973 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Androgen Antagonists
• Anilides
• Antineoplastic Agents
• CAMK2N1 protein, human
• Nitriles
• Proteins
• RNA, Small Interfering
• Receptors, Androgen
• Tosyl Compounds
• bicalutamide
• Oncogene Protein v-akt
• Calcium-Calmodulin-Dependent Protein Kinase Type 2

Topics

• Androgen Antagonists (pharmacology)
• Anilides (pharmacology)
• Antineoplastic Agents (pharmacology)
• Calcium-Calmodulin-Dependent Protein Kinase Type 2 (metabolism)
• Carcinogenesis (genetics)
• Carcinoma (genetics, metabolism, mortality)
• Cell Growth Processes (genetics)
• Drug Resistance (genetics)
• Feedback, Physiological
• Gene Expression Regulation, Neoplastic (genetics)
• Humans
• Male
• Nitriles (pharmacology)
• Oncogene Protein v-akt (metabolism)
• Prostatic Neoplasms (genetics, metabolism, mortality)
• Proteins (genetics, metabolism)
• RNA, Small Interfering (genetics)
• Receptors, Androgen (metabolism)
• Signal Transduction (genetics)
• Survival Analysis
• Tosyl Compounds (pharmacology)
• Tumor Cells, Cultured