casein-kinase-ii and Carcinoma

To investigate the expression of HPA, CK2beta and HIF-1alpha gene in nasopharyngeal carcinoma (NPC) tissues, and the correlation between their expression with the clinical characteristics of NPC and the relativity of HPA, CK2beta and HIF-1alpha gene in NPC tissues.. HPA, CK2beta and HIF-1alpha were detected with Super-Vision immunohistochemical method using antibody in 49 NPC specimens and 30 specimens with chronic nasopharyngitis tissue (CNT).. The expression of HPA, CK2beta and HIF-1alpha in NPC tissue were significantly higher than those in CNT tissue (P<0.05, separately). The expression of HPA, CK2beta and HIF-1alpha were significantly related to the TNM stage and whether recurrence or metastasis occur after treatment (P<0.05, separate ly), but there was no obvious correlation between its expression and the sex of NPC patient (P>0.05). The expression of HIF-1alpha was significantly related to the age of NPC patient (P<0.05), while HPA, CK2beta were not. The expression of HPA, CK2beta and HIF-1alpha in NPC tissue was positively correlated with each other (P<0.05, separately).. HPA, CK2beta and HIF-1alpha play synergetic role in development of NPC, which plays an important role in invasiveness,recurrence and metastasis of NPC. There could be a positive cooperation among HPA, CK2beta and HIF-1alpha in the carcinogenesis and development of NPC.

Topics: Carcinoma; Casein Kinase II; Female; Heparin Lyase; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Male; Middle Aged; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Neoplasm Staging

To investigate the expression of protein kinase CK2α (CK2α) in human thyroid disease and its relationship with thyroid cancer metastasis.. Using immunohistochemistry we measured the expression of CK2α in 76 benign and malignant human thyroid cancer tissues, including 10 pairs of papillary carcinoma tissues with or without lymph node cancerous metastasis and similarly 10 pairs of lymph nodes.. The expression of CK2α was found to be higher in thyroid carcinoma cases (papillary carcinoma, follicular carcinoma, anaplastic carcinoma and medullary carcinoma) than in ones such as chronic lymphocytic thyroiditis, nodular goiter and adenoma. These findings were also confirmed by RT-PCR and Western blotting. More strikingly, elevated expression of CK2α in thyroid papillary carcinoma tissues was not only significantly associated with lymph node cancerous metastasis and clinical stage of thyroid cancers; but also correlated with epithelial-mesenchymal transition (EMT) and high tenascin C (TNC) expression. In addition, EMT and high TNC expression in thyroid carcinoma tissues was significantly associated with lymph node cancerous metastasis.. Elevated expression of nuclear CK2α is a poor prognosis indicator in lymph node cancerous metastasis of human thyroid cancers.

Topics: Adenocarcinoma, Follicular; Adenoma; Adult; Aged; Cadherins; Carcinoma; Carcinoma, Neuroendocrine; Carcinoma, Papillary; Case-Control Studies; Casein Kinase II; Epithelial-Mesenchymal Transition; Female; Goiter, Nodular; Humans; Immunohistochemistry; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Prognosis; Tenascin; Thyroid Cancer, Papillary; Thyroid Carcinoma, Anaplastic; Thyroid Neoplasms; Thyroiditis, Autoimmune; Young Adult

Cancer is a leading cause of death worldwide. Cancer cells proliferate uncontrollably and, many cases, spread to other parts of the body. A protein historically involved in cancer is protein kinase CK2. CK2 is a serine-threonine kinase that has been involved in cell growth, cell proliferation and cell apoptosis. CK2 functions as an oncogene when overexpressed in mouse tissues, and can synergize with known oncogenes, such as ras, to induce cell transformation in cells in culture. CK2, typically the CK2α protein, is found elevated in a number of human tumors. However, we have little information on CK2α' and CK2β proteins, and scarce information on CK2 gene transcript expression. Here, we explore the expression of CK2 transcripts in primary tumor tissues using the database Oncomine in the six cancers with the highest mortality in the U.S.A. In addition, we studied the correlation between CK2 expression and overall survival using the Kaplan-Meier Plotter database in breast, ovarian, and lung cancers. We found widespread upregulation in the expression of CK2 genes in primary tumor tissues. However, we found underexpression of CK2α' transcripts in some tumors, increased CK2β transcripts in some invasive tumors, and deregulation of CK2 transcripts in some tumor precursors. There was also correlation between CK2 expression levels and patient survival. These data provides additional evidence for CK2 as a biomarker for cancer studies and as a target for cancer therapy.

Topics: Biomarkers, Tumor; Breast Neoplasms; Carcinoma; Casein Kinase II; Female; Gene Expression Regulation, Neoplastic; Humans; Lung Neoplasms; Male; Ovarian Neoplasms; Prognosis; RNA, Messenger

Protein kinase CK2 (also known as Caseine Kinase II) is an ubiquitous Ser/Thr protein kinase present in both the nucleus and cytoplasm of cells, targeting several key enzymes, growth factor receptors, transcription factors and cytoskeletal proteins. It is not only a key player in regulating cellular growth and proliferation, but also behaves as a potent suppressor of apoptosis. CK2 has been frequently found to be deregulated (mostly hyperactivated) in all cancers, prostate cancer being prominent of them. In the recent past, tumor suppressor PML (promyelocytic leukemia) has been shown to be a target of phosphorylation by CK2. This phosphorylation promotes the ubiquitin-mediated proteasomal degradation of PML thereby effectively curbing its role as a tumor suppressor. Among many others, PML has also been established to mediate its tumor suppressive role by mitigating the inactivation of active AKT (pAKT) inside the nucleus by assembling a dephosphorylating platform for nuclear pAKT. One of the immediate consequences, of this inactivation is the stabilization of FOXO3a, another well-established tumor suppressor, inside the nucleus and its downstream activities. Here, we propose a novel signaling axis apexed by deregulated CK2, dismantling the association of PML and PHLPP2 (we also report PHLPP2 to be a novel interacting partner of PML inside the nucleus), ultimately leading to the inactivation and nuclear exclusion of FOXO3a, thereby downregulating p21/p27/Bim in which degradation of PML and the concomitant stabilization of pAKT plays a cardinal part.

Topics: Apoptosis Regulatory Proteins; Bcl-2-Like Protein 11; Carcinoma; Casein Kinase II; Cell Line, Tumor; Cell Movement; Cell Nucleus; Cyclin-Dependent Kinase Inhibitor p27; Forkhead Box Protein O3; Forkhead Transcription Factors; Gene Expression Regulation, Neoplastic; Humans; Male; Membrane Proteins; Nuclear Proteins; p21-Activated Kinases; Phosphoprotein Phosphatases; Promyelocytic Leukemia Protein; Prostatic Neoplasms; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-akt; RNA, Small Interfering; Signal Transduction; Transcription Factors; Transcription, Genetic; Tumor Suppressor Proteins

Epithelial-to-mesenchymal transition (EMT) is closely linked to conversion of early-stage tumours into invasive malignancies. Many signalling pathways are involved in EMT, but the key regulatory kinases in this important process have not been clearly identified. Protein kinase CK2 is a multi-subunit protein kinase, which, when overexpressed, has been linked to disease progression and poor prognosis in various cancers. Specifically, overexpression of CK2α in human breast cancers is correlated with metastatic risk. In this article, we show that an imbalance of CK2 subunits reflected by a decrease in the CK2β regulatory subunit in a subset of breast tumour samples is correlated with induction of EMT-related markers. CK2β-depleted epithelial cells displayed EMT-like morphological changes, enhanced migration, and anchorage-independent growth, all of which require Snail1 induction. In epithelial cells, Snail1 stability is negatively regulated by CK2 and GSK3β through synergistic hierarchal phosphorylation. This process depends strongly on CK2β, thus confirming that CK2 functions upstream of Snail1. In primary breast tumours, CK2β underexpression also correlates strongly with expression of EMT markers, emphasizing the link between asymmetric expression of CK2 subunits and EMT in vivo. Our results therefore highlight the importance of CK2β in controlling epithelial cell plasticity. They show that CK2 holoenzyme activity is essential to suppress EMT, and that it contributes to maintaining a normal epithelial morphology. This study also suggests that unbalanced expression of CK2 subunits may drive EMT, thereby contributing to tumour progression.

Topics: Breast Neoplasms; Carcinoma; Casein Kinase II; Cells, Cultured; Epithelial-Mesenchymal Transition; Female; Gene Expression Profiling; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Humans; Isoenzymes; Microarray Analysis; Models, Biological; Protein Subunits; Snail Family Transcription Factors; Tissue Array Analysis; Transcription Factors; Up-Regulation

Previously, we reported that high PKCK2 activity could protect cancer cells from death receptor-mediated apoptosis through phosphorylation of procaspase-2. Because anoikis is another form of apoptosis, we asked whether PKCK2 could similarly confer resistance to anoikis on cancer cells. Human esophageal squamous cancer cell lines with high PKCK2 activity (HCE4 and HCE7) were anoikis-resistant, whereas cell lines with low PKCK2 activity (TE2 and TE3) were anoikis-sensitive. Because the cells showed different sensitivity to anoikis, we compared the expression of cell adhesion molecules between anoikis-sensitive TE2 and anoikis-resistant HCE4 cells using cDNA microarray. We found that E-cadherin is expressed only in TE2 cells; whereas N-cadherin is expressed instead of E-cadherin in HCE4 cells. To examine whether PKCK2 activity could determine the type of cadherin expressed, we first increased intracellular PKCK2 activity in TE2 cells by overexpressing the PKCK2α catalytic subunit using lentivirus and found that high PKCK2 activity could switch cadherin expression from type E to N and confer anoikis resistance. Conversely, a decrease in PKCK2 activity in HCE4 cells by knockdown of PKCK2α catalytic subunit using shRNA induced N- to E-cadherin switching and the anoikis-resistant cells became sensitive. In addition, N-cadherin expression correlated with PKB/Akt activation and increased invasiveness. We conclude that high intracellular PKCK2 activity confers anoikis resistance on esophageal cancer cells by inducing E- to N-cadherin switching.

Topics: Anoikis; Antigens, CD; Cadherins; Carcinoma; Casein Kinase II; Cell Line, Tumor; Cell Proliferation; Drug Resistance, Neoplasm; Esophageal Neoplasms; Extracellular Matrix; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; Humans; Neoplasm Invasiveness; Phosphorylation; Signal Transduction

Colorectal cancer (CRC) is one of the most common malignancies but the current therapeutic approaches for advanced CRC are less efficient. Thus, novel therapeutic approaches are badly needed. The purpose of this study is to investigate the involvement of nuclear protein kinase CK2 α subunit (CK2α) in tumor progression, and in the prognosis of human CRC.. Expression levels of nuclear CK2α were analyzed in 245 colorectal tissues from patients with CRC by immunohistochemistry, quantitative real-time PCR and Western blot. We correlated the expression levels with clinicopathologic parameters and prognosis in human CRC patients. Overexpression of nuclear CK2α was significantly correlated with depth of invasion, nodal status, American Joint Committee on Cancer (AJCC) staging, degree of differentiation, and perineural invasion. Patients with high expression levels of nuclear CK2α had a significantly poorer overall survival rate compared with patients with low expression levels of nuclear CK2α. In multi-variate Cox regression analysis, overexpression of nuclear CK2α was proven to be an independent prognostic marker for CRC. In addition, DLD-1 human colon cancer cells were employed as a cellular model to study the role of CK2α on cell growth, and the expression of CK2α in DLD-1 cells was inhibited by using siRNA technology. The data indicated that CK2α-specific siRNA treatment resulted in growth inhibition.. Taken together, overexpression of nuclear CK2α can be a useful marker for predicting the outcome of patients with CRC.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma; Casein Kinase II; Catalytic Domain; Cell Nucleus; Colorectal Neoplasms; Female; Follow-Up Studies; Gene Expression Regulation, Neoplastic; Humans; Male; Middle Aged; Nuclear Proteins; Prognosis; Young Adult

Gastric carcinoma is one of the most common malignancies in the world, yet little is known about the molecular process of its development and progression. The aims of this study are to correlate the expression of nuclear protein kinase CK2 beta subunit (CK2beta) with clinicopathologic parameters and patient survival.. Expression levels of nuclear CK2beta were analyzed in 104 gastric tissues from patients with gastric carcinoma by immunohistochemistry. A paired t test was used to analyze the differences in nuclear CK2beta expression between tumor and nontumor tissues in the same patient. A two-tailed chi (2) test was performed to determine the significance of the difference between nuclear CK2beta expression and clinicopathologic parameters. All time-to-event endpoints according to various clinicopathologic parameters were plotted by Kaplan-Meier method, and significance was then determined by univariate log-rank test. Cox proportional-hazards model was used for multivariate analysis to determine the independence of prognostic impact of nuclear CK2beta expression.. Overexpression of nuclear CK2beta was significantly correlated with depth of invasion (P = 0.042). Patients with high expression levels of nuclear CK2beta had a significantly poorer overall survival rate compared with patients with low expression levels of nuclear CK2beta (P = 0.0006). On multivariate Cox regression analysis, overexpression of nuclear CK2beta and stage were proven to be independent prognostic markers for gastric carcinoma (P = 0.0036 and 0.0005, respectively).. Overexpression of nuclear CK2beta can be a useful marker for predicting the outcome of patients with gastric carcinoma.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma; Casein Kinase II; Cohort Studies; Female; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Male; Middle Aged; Multivariate Analysis; Neoplasm Staging; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Stomach Neoplasms; Survival Analysis

The purpose of this study was to investigate the anticancer effect of aloe-emodin, an anthraquinone compound present in the leaves of Aloe vera, on two distinct human gastric carcinoma cell lines, AGS and NCI-N87. We demonstrate that aloe-emodin induced cell death in a dose- and time-dependent manner. Noteworthy is that the AGS cells were generally more sensitive than the NCI-N87 cells. Aloe-emodin caused the release of apoptosis-inducing factor and cytochrome c from mitochondria, followed by the activation of caspase-3, leading to nuclear shrinkage and apoptosis. In addition, exposure to aloe-emodin suppressed the casein kinase II activity in a time-dependent manner and was accompanied by a reduced phosphorylation of Bid, a downstream substrate of casein kinase II and a pro-apoptotic molecule. These preclinical studies suggest that aloe-emodin represents a suitable and novel chemotherapeutic drug candidate for the treatment of human gastric carcinoma.

Topics: Anthraquinones; Antineoplastic Agents, Phytogenic; Apoptosis; Apoptosis Inducing Factor; BH3 Interacting Domain Death Agonist Protein; Carcinoma; Casein Kinase II; Cell Line, Tumor; Cytochromes c; Dose-Response Relationship, Drug; Humans; Phosphorylation; Stomach Neoplasms; Time Factors

To assess the effect of small interfering RNA (siRNA) specific to protein kinase CK2a on proliferation and apoptosis of Hep-2 cell line.. siRNA expression plasmid psiRNA-hH1neo-CK2 specific to protein kinase CK2a and non-specific siRNA expression plasmid psiRNA-hH1neo-cont were constructed respectively, and then were transfected into Hep-2 cells by lipofectamine methods. Protein kinase CK2a mRNA and protein of the transfected cells were detected by reverse transcription polymerase chain reaction (RT-PCR) and Western Blot, respectively. Proliferation and apoptosis of the transfected cells were observed by methyl thiazolyl tetrazolium (MTT) method and flow cytometry (FCM), respectively.. Protein kinase CK2a mRNA and protein expressions were significantly decreased in the cells transfected with psiRNA-hH1neo-CK2 (P < 0.05). The Hep-2 cells grew slowly after transfected with psiRNA-hH1neo-CK2(P < 0.05). Obvious subdiploid peaks were found in the cells transfected with psiRNA-hH1neo-CK2 (P < 0.05).. siRNA expression plasmid specific to protein kinase CK2a suppressed the protein kinase CK2a expression and the proliferation of Hep-2, and induced apoptosis of Hep-2 cells.

Topics: Carcinoma; Casein Kinase II; Cell Line, Tumor; Cell Proliferation; Humans; Laryngeal Neoplasms; Plasmids; RNA, Messenger; RNA, Small Interfering; Transfection