casein-kinase-ii and Nasopharyngeal-Neoplasms

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

Latent Epstein-Barr virus (EBV) infection is an important causative factor in the development of several cancers, including nasopharyngeal carcinoma (NPC). The one EBV protein expressed in the nucleus of NPC cells, EBNA1, has been shown to disrupt promyelocitic leukemia (PML) nuclear bodies (NBs) by inducing the degradation of PML proteins, leading to impaired DNA repair and increased cell survival. Although EBNA1-mediated PML disruption is likely to be an important factor in the development of NPC, little is known about its mechanism. We now show that an interaction between EBNA1 and the host CK2 kinase is crucial for EBNA1 to disrupt PML bodies and degrade PML proteins. EBNA1 increases the association of CK2 with PML proteins, thereby increasing the phosphorylation of PML proteins by CK2, a modification that is known to trigger the polyubiquitylation and degradation of PML. The interaction between EBNA1 and CK2 is direct and occurs through the β regulatory subunit of CK2 and EBNA1 amino acids 387 to 394. The binding of EBNA1 to the host ubiquitin specific protease USP7 has also been shown to be important for EBNA1-mediated PML disruption. We show that EBNA1 also increases the occupancy of USP7 at PML NBs and that CK2 and USP7 bind independently and simultaneously to EBNA1 to form a ternary complex. The combined results indicate that EBNA1 usurps two independent cellular pathways to trigger the loss of PML NBs.

Topics: Binding Sites; Casein Kinase II; Cell Line, Tumor; Epstein-Barr Virus Nuclear Antigens; Herpesvirus 4, Human; Host-Pathogen Interactions; Humans; Intranuclear Inclusion Bodies; Nasopharyngeal Neoplasms; Nuclear Proteins; Phosphorylation; Promyelocytic Leukemia Protein; Protein Binding; Transcription Factors; Tumor Suppressor Proteins; Ubiquitin Thiolesterase; Ubiquitin-Specific Peptidase 7

To investigate the effect of protein kinase CK2 gene silencing on the radiosensitization in human nasopharyngeal carcinoma (NPC) cells and its possible mechanism.. RNA interference (RNAi) technique was used to down-regulate the protein kinase CK2alpha expression in 5-8F cells, and clonogenic assay was employed to observe the changes in the radiosensitivity of the cells. DNA double-strand break was assessed by immunofluorescence staining of gamma-H2AX foci, and the cell apoptosis was examined using Annexin V-FITC/PI double-staining flow cytometry.. CK2alpha protein was successfully silenced by siRNA. CK2alpha knockdown significantly decreased the clonogenic activity and increased the radiosensitivity of the NPC cells. After a 15-min exposure of the cells to 1 Gy radiation, significant difference occurred in the gamma-H2AX foci between CK2alpha knockdown cells and the control cells (P<0.01). CK2alpha silencing significantly increased the cell apoptosis after the exposure (P<0.01).. Protein kinase CK2 plays an important role in the radiosensitivity of the NPC cells, and suppression of its expression might be a potential therapeutic approach of cancer.

Topics: Animals; Annexin A5; Casein Kinase II; Cell Line, Tumor; Histones; Humans; Nasopharyngeal Neoplasms; Radiation Tolerance; RNA Interference; RNA, Small Interfering; Transfection

To investigate the effect of protein kinase CK2alpha expression on the proliferation and invasion of human nasopharyngeal carcinoma and related mechanism.. RNA interference (RNAi) was used to down-regulate the protein kinase CK2alpha expression in 5-8F cells. The biological behavior of treated cells were analyzed by MTT and in-vitro invasion assays. Cell proliferation cycle was examined by flow cytometry and the phosphorylation status of Akt protein was examined by Western blotting analysis.. CK2alpha protein was successfully silenced by siRNA. CK2alpha knockdown significantly decreased the proliferative and invasive abilities of 5-8F cells. Flow cytometry analysis showed that the percentage of cells increased in G(0)/G(1) phase but decreased in S phase. Moreover, the expression of phosphorylated Akt was down-regulated by CK2alpha silencing.. Protein kinase CK2alpha plays an important role in the proliferation and invasion of nasopharyngeal carcinoma, and may provide a potential therapeutic target against nasopharyngeal cancer.

Topics: Casein Kinase II; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Down-Regulation; Gene Expression Regulation, Neoplastic; Humans; Nasopharyngeal Neoplasms; Neoplasm Invasiveness; Phosphorylation; Proto-Oncogene Proteins c-akt; RNA Interference; RNA, Small Interfering; Transfection

Nasopharyngeal carcinoma (NPC) is a particularly common malignant disease in areas of south China and Southeast Asia. To characterize the gene expression profiling of NPC, we detected the gene expression profiles in 22 NPC and 10 nontumor nasopharyngeal epithelial tissues by complementary DNA microarray. We identified 503 genes that were significantly (P < .001) differentially regulated between NPC and nontumor nasopharyngeal epithelial tissues. The differentially expressed genes are involved in many signaling pathways, such as the Wnt, transforming growth factor-beta, and mitogen-activated protein kinase signaling pathways. The aberrant expression of the Wnt signaling pathway components, such as wingless-type MMTV integration site family, member 5A, Frizzled homolog 7, casein kinase IIbeta, beta-catenin, CREB-binding protein, and Dishevelled-associated activator of morphogenesis 2 was validated on the NPC tissue microarrays. The data suggest that the Wnt signaling pathway may be abnormally regulated in NPC, which provides insight into the molecular mechanisms of NPC.

Topics: Adolescent; Adult; Aged; beta Catenin; Casein Kinase II; Cluster Analysis; CREB-Binding Protein; Female; Frizzled Receptors; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; In Situ Hybridization; Male; Middle Aged; Nasopharyngeal Neoplasms; Oligonucleotide Array Sequence Analysis; Proto-Oncogene Proteins; Receptors, G-Protein-Coupled; RNA, Messenger; Signal Transduction; Wnt Proteins; Wnt-5a Protein