UNIPROT:P04637 - FACTA Search

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Query: UNIPROT:P04637 (p53)
77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although previous studies showed that the principal oncoprotein encoded by Epstein-Barr virus, latent membrane protein 1(LMP1), could induce the nasopharyngeal carcinoma cells in G2/M phase increased, little is known about the target molecules and mechanisms. The present study demonstrated that LMP1 could induce the accumulation of p53 protein and upregulate its transactivity in a dose dependent manner, which resulted in the decrease of the kinase activity of cdc2/cyclin B complex and inducing arrest at G2/M phase through the activation of NF-kappaB and AP-1 signaling pathways, and the effect of NF-kappaB was more obvious than that of AP-1. This study provided some significant evidence for further elucidating the molecular mechanisms that LMP1 had effects on the surveillance mechanism of cell cycle and promoting the survival of transformed cells and tumorigenesis.
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PMID:Cells in G2/M phase increased in human nasopharyngeal carcinoma cell line by EBV-LMP1 through activation of NF-kappaB and AP-1. 1286 19

To identify molecular features of neoplasms associated with EB virus, human peripheral blood lymphocytes (huPBL) were isolated from healthy volunteer donors and were transplanted intraperitoneally into SCID mice, and then huPBL/SCID mice were infected with EB virus. Serum levels of human IgG were measured by unidirectional immunodiffusion assay. Human Alu sequence and EBER-1 in tumor tissues were detected with PCR and in situ hybridization. Immunohistochemical staining was used to examine leukocyte differentiation antigens (LCA, L26, UCHL1, PS1), viral gene products (LMP1, EBNA2, BZLF1) and cellular oncoproteins (p53, C-myc, Bcl-2 and Bax). The experiments showed that tumors developed in 24 of 34 surviving huPBL/SCID mice by EBV infection. Histopathological and immunohistochemical observations demonstrated that all of the induced tumors in SCID mice were malignant lymphomas derived from human B-lymphocytes. In situ hybridization showed that tumor cells had EBV-encoded small RNA-1 (i.e. EBER-1). Alu sequence could be amplified by PCR from human genome of tumor tissues. Immunohistochemistry detected positive staining of BZLF1-encoded protein in a small population of tumor cells of almost all cases, and positive staining of LMP1 and EBNA2 only in small number of tumor cells. Human IgG could be found in the serum of 12 SCID mice on the 15th day after huPBL engraftment, and then increased with time and with the development of induced tumors in 6 mice. Positive rates of p53, C-myc, Bcl-2 and Bax expression were 83.33%, 100%, 95.83%, 91.67%, respectively, in 24 cases of the EBV-induced lymphomas. The results indicate that molecular lesions associated with the induced B-cell lymphoma involved EBV infection, expression of oncogenic viral genes, and abnormal expression of cellular oncogenes in human xenografts. Human IgG level in the serum of huPBL/SCID mice can be considered as a useful index for tumor development.
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PMID:[Molecular pathological characteristics of human B-cell lymphomas induced by Epstein-Barr virus]. 1451 11

To understand whether the p53-regulated mdm2 gene expression was altered by the Epstein-Barr virus (EBV) in nasopharyngeal carcinoma (NPC), the NPC-TW01 cell line was infected by EBV through IgA receptor-mediated endocytosis. The mdm2 gene was expressed only in a small fraction of the NPC cell population and could be enhanced in the EBV-infected (EBV+) cells. In the animals bearing EBV+ and EBV- NPC xenografts, the MDM2+ cells only appeared in clusters in both EBV+ and EBV- tumors with stronger expression in EBV+ cells. Cotransfection of pmdm2-Luc plus pSV40-p53 plus pCMV-LMP1 in the NPC-TW06 line that had p53 heterozygous point mutation showed stronger mdm2 promoter activity than cells cotransfected with pmdm2-Luc plus pSV40-p53, but no mdm2 promoter activity was seen in cells cotransfected with pmdm2-Luc plus pCMV-LMP1. Only the EBV-LMP1 but not the EBV-LMP2A gene could enhance p53 to upregulated mdm2 expression. Tumor cells in NPC biopsy specimens revealed similar mdm2 expression as in the animal model. It is concluded that although EBV can indirectly enhance mdm2 gene expression in tumor cells that express this gene, it cannot turn on or directly regulate mdm2 expression in cells that do not express this gene. In other words, EBV plays a role as an enhancer in NPC tumorigenesis.
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PMID:MDM2 expression in EBV-infected nasopharyngeal carcinoma cells. 1544 10

Epstein-Barr virus (EBV) induces CD95 expression and the CD95 gene (FAS) is regulated by NF-kappaB, STAT1, and/or p53. To understand the contribution of these factors in the regulation of CD95 by EBV in lymphoblastoid cell lines (LCLs), we cloned dominant-active IkappaBalpha, active (STAT1alpha) and inactive (STAT1beta) forms of STAT1, p53, a dominant-negative mutant of LMP1, and wild-type LMP1 into a novel double-inducible episomal vector, pRT-1. These plasmids were stably transfected either into wild-type LCLs or EREB2-5 cells, an LCL with an estrogen-regulatable EBNA2 protein. Inhibition of LMP1 signaling decreased expression of CD95, whereas overexpression of LMP1 markedly increased it. Induction of the latency III program in EREB2-5 cells correlated with activation of NF-kappaB, STAT1, and p53. CD95 expression was regulated by these 3 transcriptional systems. STAT1 and p53 activation were secondary to NF-kappaB activation. CD95 surface expression sensitized EBV-infected B cells to the induction of CD95-mediated apoptosis. In vitro inhibition of CD95-CD95 ligand interaction was found to reverse T-cell killing of EBV-infected B cells. Therefore, LMP1 activation of NF-kappaB sensitizes infected B cells to CD95-mediated apoptosis and renders EBV latency III-immortalized B cells susceptible to elimination by the immune system, contributing to the establishment of a host/virus equilibrium.
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PMID:EBV latency III immortalization program sensitizes B cells to induction of CD95-mediated apoptosis via LMP1: role of NF-kappaB, STAT1, and p53. 1631 4

T-cell non-Hodgkin's lymphomas (NHLs) represent 10% to 15% of all diagnosed lymphomas in Western countries. Various geographic frequencies of T-cell NHL have been documented, in part reflecting increased exposure to pathogenic factors such as Epstein-Barr virus (EBV). Our aims were to assess EBV and p53 expression in Argentine pediatric T-cell lymphoma and to correlate them with patients' survival. Epstein-Barr encoded RNAs (EBERs) in situ hybridization and LMP1 and p53 immunohistochemical staining were performed on formalin-fixed paraffin-embedded lymph node biopsies from 25 pediatric T-lymphoma patients. In 17 of 25 samples good-quality DNA was obtained, and EBER polymerase chain reaction was assessed to confirm in situ hybridization and immunohistochemical results. Epstein-Barr virus expression was found in 8.0% of cases. p53-positive staining was distributed in 92% of pediatric cases. Kaplan-Meier survival analysis showed that neither EBV nor p53 expression was statistically significantly associated with event-free survival. Our data showed a low frequency of EBV association with pediatric T-cell lymphoma. It seems that p53 plays an important role in proliferation in our studied population, since it is overexpressed in 92% of T-cell lymphoma cases.
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PMID:Low frequency of Epstein Barr virus association and high frequency of p53 overexpression in an Argentinean pediatric T-cell lymphoma series. 1854 Jun 92

Nasopharyngeal carcinoma (NPC) represents one of the most frequent epithelial tumours of the child in intermediate risk regions. In the Maghreb, it represents the first cancer of teenagers of 15-20 years old. The Epstein Barr virus (EBV) is the most important etiologic factor. Its role in the pathogeneses of NPC has been confirmed by several studies. Young NPCs are characterized by a low rate of EBV antibodies and a high level of LMP1 cell expression than in adult's NPC. The undifferentiated carcinoma nasopharyngeal type (UCNT) represents the most frequent histological type. Immunohistochemical analyses of North Africa early onset NPC is characterized by a weak expression of bcl-2 and p53 and a strong expression of LMP1 and c-kit what makes them different from the adult's NPC. Clinically, cervical node involvement is constantly present. Juvenile NPC is characterized by a very important locoregional extension as well as a high rate of distant metastases. More than 15% of patients had metastases at diagnosis. Radiotherapy is still the standard therapy of NPC. Only some retrospectives studies have been published to determine the benefit, the type and the timing of the chemotherapy in the treatment of juvenile NPC. Metastatic relapses constitute the main cause of death at these young patients. An improvement of the prognosis can be waited with concomitant chemotherapy and intensity modulated radiotherapy. However, randomized multi institutional studies are necessary to standardize the treatment of the NPC in childhood.
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PMID:[Juvenile nasopharyngeal carcinoma: anatomoclinic, biologic, therapeutic and evolutive aspects]. 2038 20

Nasopharyngeal carcinoma (NPC) is an unusual head and neck cancer because of its unequal geographical distribution and its consistent association with the Epstein-Barr virus (EBV). This malignant tumor poses a serious public health problem in many countries, especially in Southeast Asia and North Africa where the recorded incidence are highest. During the past decade, a growing number of studies were undertaken to define the molecular basis of NPC. However, the analysis of several clinical and biological parameters of North African and Southeast Asian NPCs has shown notable differences, suggesting that they could result from a distinct combination of etiological factors. One intriguing characteristic of North African NPC, concerns its bimodal age distribution with a secondary peak of incidence in the range of 15-25 years, not observed in Asian NPC. In this juvenile form of NPC, immuno-histochemistry assay has shown that the two key proteins controlling the apoptotic-survival balance p53 and Bcl-2 are less frequently expressed whereas the transmembrane tyrosine-kinase receptor c-kit and the main EBV oncoprotein LMP1 were more abundant. In addition, the EBV serological alterations are less informative for the diagnosis of the juvenile compared to the adult form. In addition, most North African NPCs contain EBV strains with genetic polymorphisms distinct from those described in the Southeast Asia series (predominance of F, D, H1-H2, XhoI+ and f, C, H, XhoI- respectively). In contrast, studies relating on tumor chromosomal alterations or aberrant promoter methylation result in data very similar to those obtained from the Southeast Asia series, supporting the concept of a common molecular basis for all NPC regardless of patient geographic origin.
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PMID:[North African and Southeast Asian nasopharyngeal carcinomas: between the resemblance and the dissemblance]. 2038 21

We describe 25 patients, 14 with classical Hodgkin lymphoma and 11 with non-Hodgkin lymphoma, in all of whom an excess of Langerhans cells was evident. Except for the first three cases, in which the excess of Langerhans cells was identified on routine slides, the remaining cases were disclosed by actively investigating lymphomas with excess of CD68+ histiocytes and performing CD1a and S-100 protein immunostains. Although no clonality study was performed on the Langerhans cells, we endorse the view which states that in the above association, the Langerhans cells are polyclonal. Fourteen cases of Hodgkin lymphoma with a large number of Langerhans cells were identified in a cohort of 231 classical Hodgkin lymphomas. We compared the features of classical Hodgkin lymphoma with abundant Langerhans cells with those without Langerhans cells. Our analysis reveals that Hodgkin lymphoma with Langerhans cell excess shows greater LMP1/EBV expression (P = .007) and lower p53 expression (P = .042) in the Hodgkin-Reed-Sternberg cells but is not associated with a poorer outcome.
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PMID:High content of Langerhans cells in malignant lymphoma--incidence and significance. 2047 67

To investigate the f variant of Epstein-Barr virus (EBV) in nasopharyngeal carcinogenesis, we detected the f variant in primary nasopharyngeal carcinoma (NPC), metastatic carcinoma of the lymph node (LN), and chronic inflammation of the nasopharynx from the Guangdong region. Meanwhile, we analyzed the relationship between the f variant of EBV and LMP1, Fascin, pStat3, p53, Bcl-2, and Ki-67 expression in NPC. The results showed that the f variant of EBV was found in 11 cases of primary NPCs with LN metastasis, 12 LN metastases, and 18 primary NPCs without LN metastasis. However, only one demonstrated the F/f variant in 50 cases of chronic inflammation of the nasopharynx. The expression rate of LMP1, Fascin, pStat3, p53, Bcl-2, and Ki-67 in NPC with the f or F/f variant was higher than that with the F prototype. Furthermore, there was a significantly positive correlation between the f variant of EBV and Ki-67 expression (p < 0.05). Our study suggests that the f variant of EBV may be closely related to nasopharyngeal carcinogenesis.
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PMID:The association of genomic variation of Epstein-Barr virus BamHI F fragment with the proliferation of nasopharyngeal carcinoma. 2071 17

The relationships between the expression of cyclin B1, EBV-LMP1, P53 and P16(INK4A) in Chinese classical Hodgkin lymphoma are unknown and need exploring. Samples of classical Hodgkin lymphoma from 60 Chinese patients were analyzed for the expression of cyclin B1, EBV-LMP1, P53 and P16(INK4A) proteins by immunohistochemistry. Cyclin B1 protein was overexpressed in 90.0% (54/60) of this group of classical Hodgkin lymphoma, staining mainly and strongly in cytoplasm but also sparsely and weakly in nucleus of the Hodgkin and Reed-Sternberg (HRS) cells. EBV-LMP1, P53 and P16(INK4A) were overexpressed in 85.0%, 96.7% and 71.7% of Hodgkin lymphoma, respectively. EBV-LMP1, P53 and P16(INK4A) were was noted in the nucleus of HRS cells. Microscopically, cyclin B1 and P53 staining distinguished the HRS cells from the complex background of lymphocytes. Cyclin B1 was positively correlated with EBV-LMP1(P < 0.001) and P53(P < 0.001), but was inversely related to P16(INK4A) (P < 0.05). It is suggested that overexpression of cyclin B1 could play an important role in the evolution of classical Hodgkin lymphoma, and cyclin B1 may be considered as a potential adjunct marker to identify HRS cells in diagnosis and be served as Hodgkin lymphoma-associated antigen in the near future.
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PMID:Aberrant cytoplasmic expression of cyclin B1 protein and its correlation with EBV-LMP1, P53 and P16(INK4A) in classical Hodgkin lymphoma in China. 2117 81

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