Casein kinase 2 inhibition attenuates androgen receptor function and cell proliferation in prostate cancer cells
Article first published online: 30 JAN 2012
Copyright © 2012 Wiley Periodicals, Inc.
Volume 72, Issue 13, pages 1423–1430, 15 September 2012
How to Cite
Yao, K., Youn, H., Gao, X., Huang, B., Zhou, F., Li, B. and Han, H. (2012), Casein kinase 2 inhibition attenuates androgen receptor function and cell proliferation in prostate cancer cells. Prostate, 72: 1423–1430. doi: 10.1002/pros.22493
- Issue published online: 8 AUG 2012
- Article first published online: 30 JAN 2012
- Manuscript Accepted: 2 JAN 2012
- Manuscript Received: 30 AUG 2011
- casein kinase 2;
- prostate cancer;
- androgen receptor;
- cell proliferation;
Casein kinase 2 (CK2) is constitutively active with dual specificity and exists as a hetero-tetrameric complex of α, α′, and β subunits. Its aberrant expression and elevated activity have been linked to many human cancers, including prostate cancer. As an effort to develop new chemotherapy for prostate cancers, in this study, we tested the effects of tetra-bromo-cinnamic acid (TBCA), a newly synthetic CK2-selective CK2 inhibitor, on androgen receptor (AR) transactivation, cell proliferation, and viability in multiple prostate cancer cell lines.
We utilized a comprehensive approach of a newly synthetic CK2-selective inhibitor TBCA, plus gene-specific siRNAs in multiple cell-based assays to further understand the role of CK2 in AR signaling. Alamar-blue-based cell growth assay, flow cytometry for cell cycle distribution, Luciferase report gene assay for AR transactivation, and immuno-fluorescent approach for AR nuclear localization as well as quantitative PCR assay for AR-mediated gene expression were utilized. The significance of the differences between treatment and control was analyzed using the SPSS software (SPSS, Chicago, IL).
Our data revealed that TBCA reduced cell proliferation and caused G2/M cell cycle arrest in a dose-dependent manner. Further analysis demonstrated that TBCA blocked AR nuclear translocation and gene expression. To confirm the target specificity, we used gene-specific siRNAs for both CK2α and CK2α′ subunits, and the results suggested that both CK2 catalytic subunits are involved in androgen-stimulated AR nuclear translocation and AR-mediated gene expression in prostate cancer cells.
CK2 subunits α and α′ are likely involved in AR signaling, and TBCA might be useful in the management of prostate cancers as a chemo-preventive agent in the future. Prostate 72:1423–1430, 2012. © 2012 Wiley Periodicals, Inc.