ASSOCIATION OF ELEVATED PROTEIN-KINASE CK2 ACTIVITY WITH AGGRESSIVE-BEHAVIOR OF SQUAMOUS-CELL CARCINOMA OF THE HEAD AND NECK

Background: Protein kinase CK2 (also known as casein kinase 2) is a me ssenger-independent protein serine/ threonine kinase ubiquitously dist ributed in eukaryotes. CK2 has been found to phosphorylate a wide vari ety of cytosolic and nuclear substrates which are intimately involved in regulation of DNA, RNA, and protein syn thesis, and differentiation . We therefore addressed the hypothesis that malignant transformation of upper aerodigestive tract mucosa to squamous cell carcinoma of the head and neck (SCCHN) might be associated with altered CK2 activity. M aterials and Methods: To this end, we subjected surgical specimens of SCCHN tumors and of normal oropharyngeal mucosa to subcellular fractio nation. We then quantitated CK2 activity in cytosol and nuclei of thes e specimens using a CK2-specific peptide substrate (Arg-Arg-Arg-Glu-Gl u-Glu-Thr-Glu-Glu-Glu). Results: We found that CK2 activity was signif icantly elevated in both nuclear (p < 0.0005) and cytosolic (p < 0.003 4) compartments of SCCHN tumors, relative to normal oropharyngeal muco sa. Moreover, CK2 activity in the cellular cytosolic fraction of SCCHN tumors was associated with less differentiated histologic grade (p < 0.037), positive nodal metastatic status (p < 0.056), and a poor clini cal outcome (p < 0.028). Kaplan-Meier cumulative survival analysis rev ealed greatly reduced survival in the high-CK2 activity patient group, with high statistical significance (p < 0.023). Conclusions: These pr eliminary data reveal that malignant transformation of the upper aerod igestive tract mucosa is associated with altered CK2 activity. The res ults further suggest that dysregulation of this protein kinase may pla y a significant role in the pathobiology of SCCHN, and that CK2 activi ty may be a prognostic indicator in this malignancy.