Protein Kinase CK2 Expression Predicts Relapse Survival in ERα Dependent Breast Cancer, and Modulates ERα Expression in Vitro

International Journal of Environmental Research and Public Health

Marlon D. Williams¹  Thu Nguyen¹  Patrick P. Carriere¹  Syreeta L. Tilghman²  Christopher Williams¹  Mark Edberg³  Barbara E. Hayes³  Valerie Montgomery Rice³ 

[1] College of Pharmacy, Xavier University of Louisiana, 1 Drexel Dr, New Orleans, LA 70125;Division of Basic Sciences, College of Pharmacy and Pharmaceutical Sciences, Florida Agricultural & Mechanical University, 1415 S. Martin L. King Jr. Blvd., Tallahassee, FL 32307;;College of Pharmacy, Xavier University of Louisiana, 1 Drexel Dr, New Orleans, LA 70125

关键词: CK2;    estrogen receptor (ERα);    relapse free survival;    breast cancer;   

DOI  :  10.3390/ijerph13010036

来源: mdpi

【 摘 要 】

The heterotetrameric protein kinase CK2 has been associated with oncogenic transformation, and our previous studies have shown that it may affect estrogenic signaling. Here, we investigate the role of the protein kinase CK2 in regulating ERα (estrogen receptor α) signaling in breast cancer. We determined the correlation of CK2α expression with relapse free breast cancer patient survival utilizing Kaplan Meier Plotter (kmplot.com/analysis/) to mine breast cancer microarrays repositories. Patients were stratified according to ERα status, histological grade, and hormonal therapy. Luciferase reporter assays and flow cytometry were implemented to determine the impact of CK2 inhibition on ERE-mediated gene expression and expression of ERα protein. CK2α expression is associated with shorter relapse free survival among ERα (+) patients with grade 1 or 2 tumors, as well as among those patients receiving hormonal therapy. Biochemical inhibition of CK2 activity results in increased ER-transactivation as well as increased expression among ERα (+) and ERα (−) breast cancer cell lines. These findings suggest that CK2 may contribute to estrogen-independent cell proliferation and breast tumor progression, and may potentially serve as a biomarker and pharmacological target in breast cancer.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.