Tao Wang, Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhan; Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanFollow
Shuiming Guo, Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhan; Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanFollow
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Mingchao Li, Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhan; Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanFollow
Jun Yang, Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhan; Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanFollow
Ruibao Chen, Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhan; Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanFollow
Xiaming Liu, Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhan; Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhan
Hua Xu, Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhan; Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanFollow
Shaoxin Cai, Department of Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanFollow
Hui Chen, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanFollow
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Shaohua Xu, Department of Gynecology, Shanghai First Matenity and Infant Hospital, Tongji University School of MedicineFollow
Liang Wang, Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanFollow
Zhiquan Hu, Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhan; Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanFollow
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Liping Wang, Kimmel Cancer Center, Department of Cancer Biology, Thomas Jefferson UniversityFollow
Kongming Wu, Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanFollow
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Zhangqun Ye, Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhan; Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanFollow
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Chenguang Wang, Key Laboratory of Tianjin Radiation and Molecular Nuclear Medicine; Institute of Radiation Medicine, Peking Union Medical College and Chinese Academy of Medical SciencesFollow
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Document Type

Article

Publication Date

11-15-2014

Comments

This article has been peer reviewed. It was published in: Oncotarget.

Volume 5, Issue 21, 2014, Pages 10293-10306.

The published version is available at PMID: 25296973

Copyright © 2014 Wang et al.

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.

PubMed ID

25296973

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