title: Protein Kinase CK2 Expression Predicts Relapse Survival in ERα Dependent Breast Cancer, and Modulates ERα Expression in Vitro.
abstract: 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.
authors.affiliation: College of Pharmacy, Xavier University of Louisiana, 1 Drexel Dr, New Orleans, LA 70125, USA. mwilli41@xula.edu.
authors.forename: Marlon D
authors.initials: MD
authors.lastname: Williams
authors.affiliation: College of Pharmacy, Xavier University of Louisiana, 1 Drexel Dr, New Orleans, LA 70125, USA. tnguye71@xula.edu.
authors.forename: Thu
authors.initials: T
authors.lastname: Nguyen
authors.affiliation: College of Pharmacy, Xavier University of Louisiana, 1 Drexel Dr, New Orleans, LA 70125, USA. pcarriere@msm.edu.
authors.forename: Patrick P
authors.initials: PP
authors.lastname: Carriere
authors.affiliation: Division of Basic Sciences, College of Pharmacy and Pharmaceutical Sciences, Florida Agricultural &amp; Mechanical University, 1415 S. Martin L. King Jr. Blvd., Tallahassee, FL 32307. syreeta.tilghman@famu.edu.
authors.forename: Syreeta L
authors.initials: SL
authors.lastname: Tilghman
authors.affiliation: College of Pharmacy, Xavier University of Louisiana, 1 Drexel Dr, New Orleans, LA 70125, USA. cwilli35@xula.edu.
authors.forename: Christopher
authors.initials: C
authors.lastname: Williams
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism / Q000628:therapy*; D047390:Casein Kinase II / Q000378:metabolism; D045744:Cell Line, Tumor; D018572:Disease-Free Survival; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D009364:Neoplasm Recurrence, Local / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; C570325:CSNK2A1 protein, human; D047390:Casein Kinase II
keywords: CK2; breast cancer; estrogen receptor (ERα); relapse free survival