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 messenger-independent protein serine/threonine kinase ubiquitously distributed in eukaryotes. CK2 has been found to phosphorylate a wide variety of cytosolic and nuclear substrates which are intimately involved in regulation of DNA, RNA, and protein synthesis, 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.


METHODS
To this end, we subjected surgical specimens of SCCHN tumors and of normal oropharyngeal mucosa to subcellular fractionation. We then quantitated CK2 activity in cytosol and nuclei of these specimens using a CK2-specific peptide substrate (Arg-Arg-Arg-Glu-Glu-Glu-Thr-Glu-Glu-Glu).


RESULTS
We found that CK2 activity was significantly elevated in both nuclear (p < 0.0005) and cytosolic (p < 0.0034) compartments of SCCHN tumors, relative to normal oropharyngeal mucosa. 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 clinical outcome (p < 0.028). Kaplan-Meier cumulative survival analysis revealed greatly reduced survival in the high-CK2 activity patient group, with high statistical significance (p < 0.023).


CONCLUSIONS
These preliminary data reveal that malignant transformation of the upper aerodigestive tract mucosa is associated with altered CK2 activity. The results further suggest that dysregulation of this protein kinase may play a significant role in the pathobiology of SCCHN, and that CK2 activity may be a prognostic indicator in this malignancy.
Department of Otolaryngology, University of Minnesota, Minneapolis, USA.
M
M
Gapany
R A
RA
Faust
S
S
Tawfic
A
A
Davis
G L
GL
Adams
K
K
Ahmed
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D047390:Casein Kinase II; D002467:Cell Nucleus / Q000201:enzymology; D002471:Cell Transformation, Neoplastic; D003600:Cytosol / Q000201:enzymology; D005260:Female; D006258:Head and Neck Neoplasms / Q000201:enzymology / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009092:Mucous Membrane / Q000201:enzymology; D009842:Oligopeptides; D009960:Oropharynx / Q000201:enzymology; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000032:analysis / Q000378:metabolism*; D012016:Reference Values; D013379:Substrate Specificity; D015996:Survival Rate
D014408:Biomarkers, Tumor; D009842:Oligopeptides; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases