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PubMed2006

Expression of protein kinase CK2 in astroglial cells of normal and neovascularized retina.

We previously documented protein kinase CK2 involvement in retinal neovascularization. Here we describe retinal CK2 expression and combined effects of CK2 inhibitors with the somatostatin analog octreotide in a mouse model of oxygen-induced retinopathy (OIR). CK2 expression in human and rodent retinas with and without retinopathy and in astrocytic and endothelial cultures was examined by immunohistochemistry, Western blotting, and reverse transcriptase-polymerase chain reaction. A combination of CK2 inhibitors, emodin or 4,5,6,7-tetrabromobenzotriazole, with octreotide was injected intraperitoneally from postnatal (P) day P11 to P17 to block mouse OIR. All CK2 subunits (alpha, alpha', beta) were expressed in retina, and a novel CK2alpha splice variant was detected by reverse transcriptase-polymerase chain reaction. CK2 antibodies primarily reacted with retinal astrocytes, and staining was increased around new intraretinal vessels in mouse OIR and rat retinopathy of prematurity, whereas preretinal vessels were negative. Cultured astrocytes showed increased perinuclear CK2 staining compared to endothelial cells. In the OIR model, CK2 mRNA expression increased modestly on P13 but not on P17. Octreotide combined with emodin or 4,5,6,7-tetrabromobenzotriazole blocked mouse retinal neovascularization more efficiently than either compound alone. Based on its retinal localization, CK2 may be considered a new immunohistochemical astrocytic marker, and combination of CK2 inhibitors and octreotide may be a promising future treatment for proliferative retinopathies.

Angiogenesis Inhibitors↗
PubMed2001

Localization of individual subunits of protein kinase CK2 to the endoplasmic reticulum and to the Golgi apparatus.

The protein kinase CK2 is composed of two catalytic alpha- or alpha'- and two regulatory beta-subunits. In mammalian cells there is ample evidence for the presence of individual CK2 subunits beside the holoenzyme. By immunofluorescence studies using peptide antibodies which allow us to detect the CK2alpha-, alpha'- and beta-subunits we found all three subunits to be co-localized with a 58 KDa Golgi protein which is specific for the Golgi complex. Subfractionation studies using dog pancreas cells revealed the presence of all three subunits of CK2 at the smooth endoplasmic reticulum (sER)/Golgi fraction whereas the rough endoplasmic reticulum (rER) harboured only the catalytic alpha- and alpha'-subunits. We found that the microsomal preparation from dog pancreas cells contained CK2 which phosphorylated a CK2 specific synthetic peptide and which was heparin sensitive. Furthermore, we could immunoprecipitate the CK2alpha-subunit that exhibited a kinase activity which phosphorylated a CK2 specific substrate and which was heparin sensitive. Protease digestion experiments revealed that the CK2 subunits were located on the cytosolic side of the rER and the sER/Golgi complex. Thus, we could demonstrate an asymmetric distribution of the CK2 subunits at the rER and sER/Golgi complex. Since the CK2alpha- and alpha'-subunits exhibit a substrate specificity which is different from the CK2 holoenzyme one might speculate that the asymmetric distribution of the CK2 holoenzyme and the CK2 catalytic subunits may have regulatory functions.

Animals↗
PubMed2004

[Inhibitory effect and its kinetic analysis of baicalein on recombinant human protein kinase CK2 holoenzyme].

BACKGROUND & OBJECTIVE: Protein kinase CK2 is a ubiquitous and pleiotropic Ser/Thr protein kinase in eukaryotic cells. CK2 activity has been shown to be markedly elevated in solid tumors and leukemia cells. Its alpha or alpha' gene is a protooncogene. CK2 is attracting increasing attention as a potential target for anti-neoplastic. This study was to search specific CK2 inhibitors in tumor cells through observation of the inhibitory effects of baicalein on recombinant human protein kinase CK2 holoenzyme and its kinetics in vitro. METHODS: Recombinant human protein kinase CK2 alpha' and beta subunits were cloned and expressed by gene engineering, and purified to homogeneous. These 2 subunits were mixed at equal molar ratio to reconstitute CK2 holoenzyme. The CK2 activity was evaluated by detecting radioactivity of 32P of [gamma-32P]ATP which was incorporated into the substrate in various conditions. RESULTS: Baicalein was shown to strongly inhibit the holoenzyme activity of CK2 with IC50 of 2.54 micromol/L. Kinetic studies of baicalein on CK2 showed that baicalein acted as an inhibitor of noncompetitive with ATP(KI=7.73 micromol/L) and mixed types with casein(KI=3.07 micromol/L). CONCLUSION: Baicalein is an effective inhibitor of protein kinase CK2 in vitro.

Casein Kinase II↗
PubMed2000

Antisense oligonucleotides against protein kinase CK2-alpha inhibit growth of squamous cell carcinoma of the head and neck in vitro.

BACKGROUND: Human squamous cell carcinomas of the head and neck (SCCHN) overexpress the protein kinase CK2, and elevated CK2 activity correlates with aggressive tumor behavior and poor clinical outcome. We therefore investigated whether interference with CK2 expression would inhibit SCCHN cell growth in vitro. METHODS: We targeted the catalytic (alpha) subunit of CK2 using an antisense oligodeoxynucleotide (ODN) strategy. Human Ca9-22 cells derived from SCCHN were transfected with CK2-alpha sense, nonsense, or antisense ODN; CK2 activity was measured; and the effect on CK2 activity and on cell growth was determined. RESULTS: Transfection of Ca9-22 cells with antisense CK2-alpha ODN resulted in significantly decreased CK2 kinase activity associated with nuclear chromatin and in dose-dependent growth inhibition of Ca9-22 cells in vitro. CONCLUSIONS: Interference with the protein kinase CK2 signal in SCCHN cells may offer a novel anticancer strategy for this malignancy.

Base Sequence↗
PubMed2001

Wild-type p53 inhibits protein kinase CK2 activity.

The growth suppressor protein p53 and the protein kinase CK2 are both implicated in cellular growth regulation. We previously found that p53 binds to protein kinase CK2 via its regulatory beta-subunit. In the present study, we analyzed the consequences of the binding of p53 to CK2 for the enzymatic activity of CK2 in vitro and in vivo. We found that the carboxy-terminus of p53 which is a potent transforming agent stimulated CK2 activity whereas full length wild-type p53 which is a growth suppressor inhibited the activity of protein kinase CK2. Inhibition of protein kinase CK2 by p53 was dose-dependent and was seen for various CK2 substrates. Experiments with heat-denatured p53 and the conformational mutant p53(R175H) revealed that an intact conformation of p53 seemed to be necessary. Transfection of wild-type and of mutant p53 into p53-/- cells showed that the inhibition of p53 on CK2 activity was also detectable in intact cells and specific for wild-type p53 indicating that the growth suppressing function of p53 might at least be partially achieved by down-regulation of protein kinase CK2.

Amino Acid Sequence↗
PubMed2005

CK2 binds, phosphorylates, and regulates its pivotal substrate Cdc37, an Hsp90-cochaperone.

Protein kinase CK2 phosphorylates and regulates a large number of substrates but roles of CK2 in protein kinase-mediated signal transduction systems remain largely uncertain. Cdc37 is a protein kinase-targeting molecular chaperone and its function in cooperation with Hsp90 is required for various signaling kinases. In this article, interaction between CK2 and Cdc37 is described. We present evidence indicating that phosphorylation of Cdc37 by CK2 in conserved Ser13 in the N-terminal extremity was prerequisite for the efficient binding activity of Cdc37 to protein kinases including Akt, Cdk4, MOK, and Raf1. In addition, the phosphorylation of Cdc37 by CK2 was crucial for the recruitment of Hsp90 to the protein kinase-Cdc37 complexes. We observed that a subset of CK2 was associated with Hsp90 and Cdc37 in cells. Whereas Hsp90 and Cdc37 were exclusively distributed in the cytoplasm, CK2alpha and CK2beta were localized mainly in the nucleus but also in the cytoplasm with different patterns. Moreover, direct association of Cdc37 with CK2alpha was observed in an E. coli system. Collectively, these findings indicated that a subpopulation of CK2 forms complexes with Hsp90 and Cdc37 in the cytoplasm and phosphorylates Cdc37, thus regulates the molecular chaperone activity of Cdc37. Since CK2 activity depends on Cdc37, CK2 and Cdc37 constitute a positive feedback machinery to control multiple Cdc37-dependent signaling protein kinases. The structure of Cdc37 and physiological importance of the CK2-Cdc37 interaction are discussed.

Amino Acid Sequence↗
PubMed2005

B23 is a downstream target of polyamine-modulated CK2.

Our previous studies have shown that the overexpression of ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine biosynthesis, increases the enzymatic activity of the polyamine-responsive enzyme casein kinase 2 (CK2). Because CK2 is known to preferentially associate with the nuclear matrix in response to other trophic stimuli, we investigated the effects of ODC overexpression on CK2 localisation and on the CK2-mediated phosphorylation of a known CK2 substrate, the nucleolar phosphoprotein B23. Immunofluorescence analysis of CK2 and B23 in primary keratinocytes revealed that ODC overexpression resulted in the colocalisation of CK2 with B23 at the nucleolar borders. ODC overexpression also increased CK2 kinase activity 2-fold at the nuclear matrix, a response which could be abrogated by treatment of K6/ODC transgenic keratinocytes with the ODC inhibitor alpha-difluoromethylornithine (DFMO). Levels of B23 protein were also elevated in ODC-overexpressing cells compared to normal cells or transgenic cells treated with DFMO. This increase in protein level was neither due to an increase in steady-state mRNA levels, nor was it due to increased stability of B23 protein. Phosphorylation of B23 was also increased in ODC-overexpressing cells, and this increased phosphorylation could be blocked by treatment of the cells with the CK2 kinase inhibitors apigenin or 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB). These data suggest that B23 may be a downstream effector of polyamines via phosphorylation by the protein kinase CK2.

Animals↗
PubMed2005

Primary and secondary interactions between CK2alpha and CK2beta lead to ring-like structures in the crystals of the CK2 holoenzyme.

Protein kinase CK2 predominantly exists as a heterotetrameric holoenyzme consisting of two catalytic subunits (CK2alpha) and two non-catalytic subunits (CK2beta). Early investigations which we review here had revealed the presence of two types of contacts between CK2alpha and CK2beta: a primary interaction responsible for the stability of the CK2 holoenzyme and stimulatory for the catalytic activity, and a secondary interaction which is inhibitory and in which the acidic loop of CK2beta associates with the basic stretch and the (p+1)-loop of CK2alpha. At the end of the last decade both types of interactions were assumed to occur within the same tetrameric complex. The CK2 holoenyzme structure, however, suggested that the secondary interactions must happen between different CK2 tetramers. Such a behaviour should lead to higher-ordered aggregates consistent with several previous reports about a distinct aggregation propensity of CK2. We demonstrate here that in the CK2 holoenzyme crystals contacts between different CK2 tetramers exists which provide structural details of the secondary CK2alpha/CK2beta interactions. These mainly ionic interactions lead to trimeric rings of CK2 holoenzymes in the crystal. In these rings each CK2 tetramer possesses one CK2alpha subunit open for substrate binding and another one whose active site is blocked by a secondary contact with CK2beta from a neighbouring tetramer. This observation fits to previous findings that salt-sensitive ring-like aggregates of CK2 holoenzymes can exist which possess significant catalytic activity. Furthermore it suggests that earlier ideas about a regulatory role of the enzyme's aggregation propensity may be worth to be revitalised.

Binding Sites↗
PubMed2003

Protein kinase CK2: structure, regulation and role in cellular decisions of life and death.

Protein kinase CK2 ('casein kinase II') has traditionally been classified as a messenger-independent protein serine/threonine kinase that is typically found in tetrameric complexes consisting of two catalytic (alpha and/or alpha') subunits and two regulatory beta subunits. Accumulated biochemical and genetic evidence indicates that CK2 has a vast array of candidate physiological targets and participates in a complex series of cellular functions, including the maintenance of cell viability. This review summarizes current knowledge of the structural and enzymic features of CK2, and discusses advances that challenge traditional views of this enzyme. For example, the recent demonstrations that individual CK2 subunits exist outside tetrameric complexes and that CK2 displays dual-specificity kinase activity raises new prospects for the precise elucidation of its regulation and cellular functions. This review also discusses a number of the mechanisms that contribute to the regulation of CK2 in cells, and will highlight emerging insights into the role of CK2 in cellular decisions of life and death. In this latter respect, recent evidence suggests that CK2 can exert an anti-apoptotic role by protecting regulatory proteins from caspase-mediated degradation. The mechanistic basis of the observation that CK2 is essential for viability may reside in part in this ability to protect cellular proteins from caspase action. Furthermore, this anti-apoptotic function of CK2 may contribute to its ability to participate in transformation and tumorigenesis.

Animals↗
PubMed1997

Ornithine decarboxylase expression leads to translocation and activation of protein kinase CK2 in vivo.

Ornithine decarboxylase (ODC) is the key initial enzyme in the biosynthesis of polyamines. Since polyamines have been shown to enhance protein kinase CK2 activity in vitro, ODC was overexpressed to examine the role of polyamines in CK2 regulation in vivo. Infection of Balb/MK cells with an ODC retrovirus to elevate ODC and polyamine levels increased overall protein phosphorylation as well as CK2 protein levels and enzyme activity in mimosine- or nocodazole- arrested cells. Immunofluorescence microscopy and enzyme analyses of subcellular fractions from ODC-overexpressing cells demonstrated translocation of CK2 from the cytoplasm to the nucleus with no apparent loss of cytoplasmic CK2 activity, suggesting polyamine activation of the remaining cytoplasmic enzyme. Similarly, K6/ODC transgenic mice exhibited higher ODC and CK2 enzyme activities than their normal littermates. ODC-immunostained cells in the transgenic skin also stained intensely for CK2 protein. Primary cultures of K6/ODC keratinocytes also exhibited increased ODC and CK2 enzyme activities compared with those from normal littermates. However, the addition of difluoromethylornithine, a specific ODC inhibitor, to the transgenic keratinocytes reduced both intracellular polyamine levels and CK2 enzyme activity. These results suggest that polyamines regulate the CK2 enzyme by affecting its cellular distribution as well as its enzyme activity and levels.

Animals↗
PubMed2000

A potential role of nuclear matrix-associated protein kinase CK2 in protection against drug-induced apoptosis in cancer cells.

Protein kinase CK2 (CK2) has long been implicated in the regulation of cell growth and proliferation. Its activity is generally elevated in rapidly proliferating tissues, and nuclear matrix (NM) is an important subnuclear locale of its functional signaling. In the prostate, nuclear CK2 is rapidly lost commensurate with induction of receptor-mediated apoptosis after growth stimulus withdrawal. By contrast, chemical-induced apoptosis in prostate cancer and other cells (by etoposide and diethylstilbestrol) evokes an enhancement in CK2 associated with the NM that appears to be because of translocation of CK2 from the cytoplasmic to the nuclear compartment. This shuttling of CK2 to the NM may reflect a protective response to chemical-mediated apoptosis. Supporting evidence for this was obtained by employing cells that were transiently transfected with various expression plasmids of CK2 (thereby expressing additional CK2) prior to treatment with etoposide or diethylstilbestrol. Cells transfected with the CK2alpha or CK2alphabeta showed significant resistance to chemical-mediated apoptosis commensurate with the corresponding elevation in CK2 in the NM. Transfection with CK2beta did not demonstrate this effect. These results suggest, for the first time, that besides the commonly appreciated function of CK2 in cell growth, it may also have a role in protecting cells against apoptosis.

Adenocarcinoma↗
PubMed2001

Urokinase-dependent human vascular smooth muscle cell adhesion requires selective vitronectin phosphorylation by ectoprotein kinase CK2.

Urokinase (uPA)- and urokinase receptor (uPAR)-dependent cell adhesion to the extracellular matrix protein vitronectin (Vn) is an important event in wound healing, tissue remodeling, immune response, and cancer. We recently demonstrated that in human vascular smooth muscle cells (VSMC) uPA/uPAR are functionally associated with the ectoprotein kinase casein kinase-2 (CK2). We now asked whether CK2 regulates uPA-dependent cell adhesion to Vn, since the latter is a natural CK2 substrate. We found that Vn is indeed selectively phosphorylated by CK2 and that this phosphorylation is uPA-regulated in VSMC. Vn induces release of ecto-CK2 from the cell surface via a process termed as "shedding." CK2-mediated Vn phosphorylation was decisive for the uPA-dependent VSMC adhesion. Specific inhibition of CK2 completely abolished the uPA-induced cell adhesion to Vn. This effect was specific for cell adhesion to Vn and required participation of both uPAR and alpha(v)beta(3) integrins as adhesion receptors. CK2 localization at the cell surface was highly dynamic; Vn induced formation of clusters where CK2 colocalized with uPAR and alpha(v)beta(3) integrins. These results indicate that the uPA-dependent VSMC adhesion is a function of selective Vn phosphorylation by the ectoprotein kinase CK2 and suggest a regulatory role for Vn phosphorylation in the uPA-directed adhesive process.

Casein Kinase II↗
PubMed2004

Protein kinase CK2 as regulator of cell survival: implications for cancer therapy.

Recent studies have generated sufficient information to warrant a consideration of protein kinase CK2 as a potential target for cancer therapy. CK2 is a ubiquitous and highly conserved protein serine/threonine kinase that has long been considered to play a role in cell growth and proliferation. It is essential for cell survival, and considerable evidence suggests that it can also exert potent suppression of apoptosis in cells. This is important since the cancer phenotype is characterized by deregulation of not only proliferation but also of apoptosis. In normal cells, the level of CK2 appears to be tightly regulated, and cells resist a change in their intrinsic level of CK2. However, in all the cancers that have been examined an elevation of CK2 has been observed. Further, it appears that modest deregulation in the CK2 expression imparts a potent oncogenic potential to the cells. Disruption of CK2 by treatment of cells with antisense CK2 results in induction of apoptosis in a time and dose-dependent manner. Thus, we propose that down-regulation of CK2 by employing specific strategies to deliver antisense CK2 in vivo could have a potential role in cancer therapy.

Animals↗
PubMed2001

FAS-associated factor 1 interacts with protein kinase CK2 in vivo upon apoptosis induction.

We show here that in several different cell lines protein kinase CK2 and Fas-associated factor 1 (FAF1) exist together in a complex which is stable to high monovalent salt concentration. The CK2/FAF1 complex formation is significantly increased after induction of apoptosis with various DNA damaging agents. Interestingly this effect is only seen in cell lines with an embryonic origin and not when cells have entered a differentiated state. It is further shown that the CK2 specific phosphorylation sites in the FAF1 molecule, i.e. serines 289 and 291 influence this complex formation. Mutation of the CK2 phosphorylation sites in the FAF1 molecule to alanine leads to a 1.5 to 2.0-fold higher association between CK2 and FAF1. Since the CK2 activity did not increase concomitantly with the complex formation we conclude that the FAF1 becomes to the CK2 enzyme so that a normal enzyme catalysis does not take place anymore. Subcellular localization experiments involving CK2 subunits and FAF1 show a co-localization of both CK2 subunits and FAF1 in the peri-nuclear cytoplasm. The majority of CK2 subunits is found in the nucleus. FAF1 is also found in the nucleoli. The results obtained further support the view that protein kinase CK2 plays an important role in certain steps of apoptosis.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Response of cancer cells to molecular interruption of the CK2 signal.

Protein kinase CK2 is one of the key cellular signals for cell survival, growth, and proliferation. It is has been observed to be elevated in various cancers that have been examined. Various observations suggest that moderate dysregulation of CK2 may profoundly influence the cell response. We have examined the effects of interfering with the CK2 signal in various cancer cell lines by employing antisense oligodeoxynucleotides (ODN) against the alpha and beta subunits of CK2. Our results demonstrate that antisense CK2-alpha and antisense CK2-beta ODNs markedly influence cell viability of these cancer cells in a dose and time-dependent manner. Antisense CK2-alpha was slightly more effective than antisense CK2-beta in most of the cells tested. The efficacy of the antisense ODN seemed to vary with the cell type; however, in all cases potent induction of apoptosis was observed. Significantly, the effects of the antisense ODN on the CK2 activity in the nuclear matrix were relatively small compared to the much stronger induction of apoptosis in cells. This suggests that modest downregulation of CK2 can evoke a much greater apoptotic response in cancer cells.

Apoptosis↗
PubMed1994

A historical view of protein kinase CK2.

The enzyme termed nowadays protein kinase CK2 was first described in liver extracts (as a mixture with protein kinase CK1), using casein as artificial substrate, by Burnett and Kennedy (1954). In 1960 it was shown that such casein/phosvitin phosphorylating activity was ubiquitous and distinct from phosphorylase kinase, i.e., the only other protein kinase known at that time. CK1 and CK2 were distinguished from each other at the end of the sixties, and during the seventies CK2 was purified to homogeneity in several laboratories and thoroughly characterized as far as its subunit structure (alpha 2 beta 2), site specificity, and in vitro responsiveness to various effectors were concerned. The first endogenous substrate for CK2 (eIF-3) was described in 1976, but it was during the eighties that it became clear that CK2 is a pleiotropic protein kinase committed with the phosphorylation of a myriad of cellular targets. More than 100 CK2 substrates are known, sharing typical phosphoacceptor sites specified by multiple acidic residues on the C terminal side of Ser/Thr. The definition of the primary structure of CK2 catalytic subunit, in 1987, definitely included CK2 in the big family of eukariotic protein kinases. The growing interest for CK2 is accounted for by its unusual properties, by the increasing number of its substrates, and by several coincidental arguments suggesting that this pleiotropic protein kinase plays a fundamental role in cellular regulation. A major and intriguing problem concerning CK2 is its apparent lack of regulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1994

Mechanism of intracellular regulation of protein kinase CK2: role of stimulus-mediated subnuclear association.

In our studies of protein kinase CK2, or casein kinase 2, we have focused on its regulation in relation to altered genomic activity in response to androgen action (through the function of the androgen receptor) in the male accessory sex gland, the prostate. We have documented that androgens exert a profound effect on CK2 in the prostate. Investigation of androgenic regulation of the molecular expression of prostatic CK2 suggested that CK2 gene transcription, although substantial in the prereplicative phase of cell proliferation, is not an early event in androgen action. The lack of rapid transcriptional regulation of CK2 by androgens suggested an alternative mechanism for our original observations on the early regulation of CK2-mediated reactions. A rigorous analysis of the CK2 in different compartments of the prostatic cell has suggested its differential regulation. For example, androgen withdrawal results in a rapid loss of CK2 protein and activity in the prostatic cell nucleus, whereas the activity and protein in the cytosol undergoes a slow decline over several days. A single dose of 5 alpha-dihydrotestosterone (5 alpha-DHT) given to 6-d castrated animals results in an increase in nuclear enzymatic activity as well as immunoreactive CK2 protein within 1 h, while a concomitant decrease is apparent in the cytosolic fraction. Within the nucleus, there appears to be a differential androgenic regulation of CK2 such that the enzyme associated with chromatin and nuclear matrix (NM) demonstrates a substantially greater androgen sensitivity than the enzyme in the nucleoplasm.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1995

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. 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.

Adult↗