Protein Kinase CK2 is a hetero-tetrameric serine/threonine kinase which has been shown to have increased expression in most types of cancer. Previous studies have identified roles for CK2 in transcriptional regulation, proliferation and survival, as well as in epithelial mesenchymal transition. Our previous studies have shown that CK2 is responsible for the phosphorylation of the estrogen receptor (ERα) at two previously unidentified sites. Here we sought to delineate the specific functions of CK2 in ERα (+) luminal and ERα (−) basal-like breast cancer. Breast tissue microarrays studies show that CK2 is expressed in both ERα (+) and ERα (−) breast tumors. In ER dependent cell lines, inhibition of CK2 causes a substantial inhibition of transcriptional activity in luciferase reporter assays. Furthermore, CK2 was found to interact with the promoters of estrogen responsive genes in an ER-dependent fashion. Despite the selective effects on ER dependent gene expression, inhibition of CK2 attenuated proliferation/ cell viability both ERα (+) and ERα (−) cell lines, suggesting that CK2 may have distinct roles in the function of specific breast cancer cell phenotypes. Indeed, Inhibition of CK2 caused cell-type specific changes in the expression of vimentin and E-cadherin, as determined by flow cytometry, as well as cell morphology. Taken together, these studies suggest that CK2 utilizes multiple molecular mechanisms to promote tumorigenesis. Inhibition of CK2 may be a viable therapeutic targeting strategy for treatment of patients with ERα (+) and ERα (−) breast tumor phenotypes.

Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):B67.