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Association of Elevated Protein Kinase CK2 Activity with Aggressive Behavior of Squamous Cell Carcinoma of the Head and Neck

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Abstract

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 aero-digestive tract mucosa to squamous cell carcinoma of the head and neck (SCCHN) might be associated with altered CK2 activity.

Materials and 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.

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Acknowledgments

The authors wish thank biostatistician, Dr. Bruce Lindgren, for assistance with statistical design and analyses, and David Lambert for his technical assistance. This work was supported in part by the American Academy of Otolaryngology, Head & Neck Surgery Research Training Award (ARTA), the Medical Research Fund of the U.S. Department of Veterans Affairs, and NCI Research Grant CA-15062. Portions of this work were presented at the Annual Meeting of the American Association for Cancer Research, 1995, and at the American Society for Head and Neck Surgery 36th Annual Meeting, 1994.

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Authors and Affiliations

  1. Departments of Otolaryngology and Head & Neck Surgery, University of Minnesota, Minneapolis, Minnesota, USA

    Markus Gapany, Russell A. Faust & George L. Adams

  2. Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, USA

    Sherif Tawfic & Khalil Ahmed

  3. Cellular and Molecular Biochemistry Research Laboratory (151), VA Medical Center, One Veterans Drive, Minneapolis, Minnesota, 55417, USA

    Alan Davis & Khalil Ahmed

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  1. Markus Gapany
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  2. Russell A. Faust
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  5. George L. Adams
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  6. P. Leder
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  7. Khalil Ahmed
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Gapany, M., Faust, R.A., Tawfic, S. et al. Association of Elevated Protein Kinase CK2 Activity with Aggressive Behavior of Squamous Cell Carcinoma of the Head and Neck. Mol Med 1, 659–666 (1995). https://doi.org/10.1007/BF03401606

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