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

被引:103
作者
GAPANY, M
FAUST, RA
TAWFIC, S
DAVIS, A
ADAMS, GL
AHMED, K
机构
[1] DEPT VET AFFAIRS MED CTR,CELLULAR & MOLEC BIOCHEM RES LAB,MINNEAPOLIS,MN
[2] UNIV MINNESOTA,DEPT OTOLARYNGOL & HEAD & NECK SURG,MINNEAPOLIS,MN 55455
[3] UNIV MINNESOTA,DEPT LAB MED & PATHOL,MINNEAPOLIS,MN 55455
关键词
D O I
10.1007/BF03401606
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 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. 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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页码:659 / 666
页数:8
相关论文
共 29 条
[1]  
AARONSON SA, 1991, SCIENCE, V245, P1146
[2]   ASSOCIATION OF CASEIN KINASE-2 WITH NUCLEAR CHROMATIN IN RELATION TO ANDROGENIC REGULATION OF RAT PROSTATE [J].
AHMED, K ;
YENICE, S ;
DAVIS, A ;
GOUELI, SA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (10) :4426-4430
[3]  
AHMED K, 1994, CELL MOL BIOL RES, V40, P1
[4]  
BATSAKIS JG, 1990, TUMORS HEAD NECK CLI, P144
[5]   ONCOGENES AND SIGNAL TRANSDUCTION [J].
CANTLEY, LC ;
AUGER, KR ;
CARPENTER, C ;
DUCKWORTH, B ;
GRAZIANI, A ;
KAPELLER, R ;
SOLTOFF, S .
CELL, 1991, 64 (02) :281-302
[6]  
COLTRERA MD, 1993, AM J PATHOL, V141, P817
[7]  
CRISSMAN JD, 1989, AM J SURG PATHOL, V13, P5
[8]  
DAYAMAKIN M, 1994, CANCER RES, V54, P2262
[9]  
DEVESA SS, 1987, J NATL CANCER I, V4, P701
[10]   THE REGULATION OF TRANSCRIPTION BY PHOSPHORYLATION [J].
HUNTER, T ;
KARIN, M .
CELL, 1992, 70 (03) :375-387