Expression of Epstein-Barr virus genes in EBV-associated gastric carcinomas

AIM: To understand the expression of latent and lytic genes of Epstein-Barr virus (EBV) in EBV-associated gastric carcinoma (EBVaGC) and to explore the relationship between EBV-encoded genes and development of EBVaGC at molecular level.METHODS: One hundred and seventy-two gastric carcinoma tissues and 172 corresponding para-carcinoma tissues were tested for EBV genome by polymerase chain reaction (PCR)-Southern blotting. EBV-encoded small RNA (EBER)1 of the PCR positive specimens was detected by in situ hybridization (ISH). Gastric carcinomas with positive EBER1signals were classified as EBVaGCs. RT-PCR and Southern hybridization were applied to the detection of expression of nuclear antigen (EBNA) promoters (Qp, Wp and Cp),EBNA 1 and EBNA 2, latent membrane proteins (LMP) 1,2A and 2B and lytic genes (immediate early genes BZLF1and BRLF1, early genes BARF1 and BHRF1, late genes BcLF1and BLLF1) in EBVaGCs.RESULTS: Eleven EBV positive samples existed in gastric carcinoma tissues (6.39%). No EBV positive sample was found in corresponding para-carcinoma tissues. The difference between EBV positivity in carcinoma tissues and corresponding para-carcinoma tissues was significant(x2 = 9.0909, P = 0.0026). Transcripts of Qp and EBNA1were detected in all the 11 EBVaGCs, while both Wp and Cp were silent. EBNA2, LMP1 and LMP2B mRNA were absent in all the cases, while LMP2A mRNA was detected in 4 of the 11 cases. Of the 11 EBVaGCs, 7 exhibited BcLF1 transcripts and 2 exhibited BHRF1 transcripts. The transcripts of BZLF1and BARF1 were detected in 5 cases, respectively. No BLLF1and BRLF mRNA were detected.CONCLUSION: The latent pattern of EBV in gastric carcinoma corresponds to the latency Ⅰ/Ⅱ. Some lyric infection genes are expressed in EBVaGCs tissues. BARF1 and BHRF1genes may play an important role in tumorigenesis of gastric carcinoma.

Clinical and pathological characterization of epstein-barr virus-associated gastric carcinomas in portugal

AIM To determine the prevalence of epstein-barr virus(eb V)-associated gastric carcinomas in the North Region of Portugal and to study its clinicopathological characteristics. METHODS We have performed a retrospective study including a total of 179 consecutive patients with gastric cancer(GC) submitted to gastrectomy during 2011 at the Portuguese Oncology Institute of Porto. Clinical and pathological data was collected from individual clinical records and inserted on a database with unique codification. Tumour tissues were collected from the institutional tumour bank. eb V was detected by in situ hybridization for the detection of eb V-encoded small RNAs(ebe Rs) and eb V latent proteins(LMP1 and LMP2 A) were detected by immunohistochemistry.RESULTS The analysis showed that eb V-associated gastric carcinomas(eb Va GC) represents 8.4%(15/179) of all GC cases, with a significant differential distribution among histological types(P < 0.001): 100%(3/3) of medullary carcinomas, 100%(1/1) of adenosquamous carcinoma, 8.7%(8/92) of tubular adenocarcinomas, 8.0%(2/25) of mixed carcinomas and 2%(1/51) in poorly cohesive carcinomas. The analysis revealed a higher predominance of eb Va GC in the upper third and middle(cardia, fundus and body) of the stomach(P = 0.041), a significant lower number of regional lymph nodes invasion(P = 0.025) and a tendency for better prognosis(P = 0.222). eb V latent protein expression revealed that all eb Va GC cases were LMP1-negative, nevertheless 6 cases(40%) expressed LPM2 A, which reveals that these cases show a distinct eb V-Latency profile(latency II-like).CONCLUSION eb Va GC represents 8.4% of all GC in the North Region of Portugal. The eb V-infected patients have specific clinic-pathological features that should be further explored to develop new strategies of management and treatment.

Epigenetic dysregulation in Epstein-Barr virus-associated gastric carcinoma: Disease and treatments

Epstein-Barr virus(EBV)-associated gastric carcinoma(EBVaGC)comprises nearly 10%of gastric carcinoma cases worldwide.Recently,it was recognised to have unique clinicopathologic characteristics,including male predominance,lower rates of lymph node involvement,and better prognosis.EBVaGC is further characterised by abnormal hypermethylation of tumour suppressor gene promoter regions,causing down-regulation of their expression.In the present review,we critically discuss the role of EBV in gastric carcinogenesis,summarising the role of viral proteins and microRNAs with respect to aberrant methylation in EBVaGC.Given the role of epigenetic dysregulation in tumourigenesis,epigenetic modifiers may represent a novel therapeutic strategy.

Association of single nucleotide polymorphism rs2065955 of the filaggrin gene with susceptibility to Epstein-Barr virus-associated gastric carcinoma and EBV-negative gastric carcinoma

The relationship between the Filaggrin gene(FLG) rs2065955 polymorphism and susceptibility to Epstein-Barr virus(EBV)-associated gastric carcinoma(EBVa GC) and EBV-negative gastric carcinoma(EBVn GC) was investigated in Shandong Province,China.We detected the FLG rs2065955 genotype and allele distribution by using PCR and restriction fragment length polymorphism(RFLP) in 64 EBVa GC,82 EBVn GC,and 111 normal control samples.Immunohistochemistry was used to detect the level of FLG protein in 35 EBVa GC and 51 EBVn GC tumor tissues.Compared with normal controls,the genotype CC and allele C of FLG rs2065955 showed higher frequency in EBVa GC and EBVn GC.There was no significant difference between EBVa GC and EBVn GC in allele distribution of FLG rs2065955,but the genotype CC was found more frequently in EBVa GC than in EBVn GC.The risk of developing either EBVa GC or EBVn GC in genotype CC was higher than in other genotypes.Furthermore,genotype CC of FLG rs2065955 may contribute more to the risk of developing EBVa GC than EBVn GC.There was no significant difference in the expression level of FLG protein between EBVa GC and EBVn GC.In conclusion,the FLG rs2065955 polymorphism was significantly related to gastric carcinoma.Allele C of FLG rs2065955 could be a risk factor for EBVa GC or EBVn GC,while genotype CC of FLG rs2065955 was especially associated with EBVa GC.

Meta-analysis of the relationship between Epstein-Barr virus infection and clinicopathological features of patients with gastric carcinoma

Epstein-Barr virus (EBV) infection has been causally associated with occurrence of many malignant neoplasms. EBV-encoded small RNAs (EBERs) have been detected from about 10% of gastric carcinoma tissue cells, suggesting that EBV infection is associated with the development of gastric carcinoma. The present study pooled the data from the papers concerning EBV-related gastric cancers and performed a meta-analysis of 22 research papers. Among these papers, a total of 5475 cases with gastric cancer were enrolled, of whom 411 cases were found EBV-positive, with the EBV-positive rate being 7.5%. Among the EBV-positive gastric cancer cases, the detection rate was 11.1% in males and 3.0% in females. Compared with EBV-negative gastric cancer, EBV-positive gastric cancer had less lymph node metastasis. Based on the histological typing, of the EBV-positive gastric cancers, the diffuse type was 8.1%, and intestinal type was 8.0%. The examined specimen types included stored paraffin blocks and fresh surgically removed specimens, their EBV positive rates were 7.9% and 6.5% respectively. In terms of geographical distribution, the detection rate of EBV-positive gastric cancer was 9.4% in America, 6.1% in Asia and 9.1% in Europe. Meta-analysis showed that EBV infection occurred only in gastric cancer tissue cells and was significantly associated with the patients’ gender, lymph node metastases, and the location where tumor tissue generated and geographical distribution (P<0.05), but was not significantly associated with the patients’ histological types of tumor and the types of specimens (P>0.05). These results suggested that EBV-positive gastric cancer has distinct clinicopathological features.

Suicide gene therapy of hepatocellular carcinoma and delivery procedure and route of therapeutic gene in vivo

Objective: To study the induction of sensitivity toganciclovir (GCV) or acyclovir (ACV) in humanhepatocellular carcinoma (HCC) cell line trans-ferred by an Epstein-Barr virus (EBV)-based repli-con expression vector carrying the herpes simplex vi-rus thymidine kinase (HSV-tk) gene, including kill-ing and "bystander" effect, and also the gene delive-ry procedure and route of gene therapy in vivo forHCC.Methods: Liposome-entrapped plasmid pDR2/tk wastransferred into HCC cells, and then different con-centrations of GCV or ACV were added. The trans-ferred cells were mixed with untransferred HCC cellsin different proportion and 200 μmol/L GCV wasthen added into each well. After 72 hours, all sam-ples were measured by MTT colorimetric assay. AnEBV-based plasmid eukarotic expression vector car-rying IL-2 cDNA was used. Three models of gene di-rect injection in the local liver, injection through theportal vein, and injection through the embolized he-patic artery were established in closed Wister rats.For each model, two subgroups, injected either na-ked plasmid DNA or lipofectin-plasmid complex wereincluded. The expression of the IL-2 gene was regu-larly examined immunohistochemically.Results: GCV or ACV could apparently kill thetransferred HCC cells at a concentration of 0. 2μmol/L. The inhibition rate was changed with dif-ferent drug concentrations. The "bystander" effectwas obviously induced at a transferred to untrans-ferred HCC cells ratio of 1:5. IL-2 gene expressionwas observed in liver cells of all animals on day 3,which reached peak within 3-7 days, and declined af-ter day 7. Injection of naked plasmid DNA throughthe hepatic artery plus embolization obtained a bestexpression.Conclusions: EBV-based vector is suitable for carry-ing suicide gene therapy for hepatocellular carcino-ma. Gene direct delivery in vivo combined with in-terventional surgery can be used to treat hepatocellu-lar carcinoma.

Comprehensive profiling of EBV gene expression in nasopharyn- geal carcinoma through paired-end transcriptome sequencing

The latent expression pattern of Epstein-Barr Virus （EBV）igenes in nasopharyngeal carcinoma （NPC） has been extensively investigated, and the expression of several lytic genes in NPC has been reported. However, comprehensive information through EBV transcriptome analysis in NPC is limited. We performed paired-end RNA-seq to systematically and comprehensively characterize the expression of EBV genes in NPC tissue and C666-1 NPC cell line, which consistently carries EBV. In addition to the transcripts restricted to type II latency infection, the type Ⅲ latency EBNA3s genes and a substantial number of lytic genes, such as BZLF1, BRLF1, and BMRF1, were detected through RNA-seq and were further verified in C666-1 cells and NPC tissue through real- time PCR. We also performed clustering analysis to classify NPC patient groups in terms of EBV gene expression, which presented two subtypes of NPC samples. Results revealed interesting patterns of EBV gene expression in NPC patients. This clustering was correlated with many signaling pathways, such as those related to heterotrimeric G-protein signaling, inflammation mediated by chemokine and cytokine signaling, ribosomes, protein metabolism, influenza infection, and ECM-receptor interaction. Our combined findings suggested that the expression of EBV genes in NPC is restricted not only to type II latency genes but also to type Ⅲ latency and lyric genes. This study provided further insights into the potential role of EBV in the development of NPC.

Oncogenic induction of cellular high CpG methylation by Epstein-Barr Barr virus in malignant epithelial cells

Epstein-Barr virus(EBV)is a well-known human herpesvirus associated with virtually all nasopharyngeal carcinoma(NPC)and^10%of gastric cancer(GC)worldwide.Increasing evidence shows that acquired genetic and epigenetic alterations lead to the initiation and progression of NPC and GC.However,even deep whole exome sequencing studies showed a relatively low frequency of gene mutations in NPC and EBV-associated GC(EBVa GC),suggesting a predominant role of epigenetic abnormities,especially promoter Cp G methylation,in the pathogenesis of NPC and EBVa GC.High frequencies of promoter methylation of tumor suppressor genes(TSGs)have been frequently reported in NPC and EBVa GC,with several EBV-induced methylated TSGs identified.Further characterization of the epigenomes(genome-wide Cp G methylation profile—methylome)of NPC and EBVa GC shows that these EBV-associated tumors display a unique high Cp G methylation epigenotype with more extensive gene methylation accumulation,indicating that EBV acts as a direct epigenetic driver for these cancers.Mechanistically,oncogenic modulation of cellular Cp G methylation machinery,such as DNA methyltransferases(DNMTs),by EBV-encoded viral proteins accounts for the EBV-induced high Cp G methylation epigenotype in NPC and EBVa GC.Thus,uncovering the EBV-associated unique epigenotype of NPC and EBVa GC would provide new insight into the molecular pathogenesis of these unique EBVassociated tumors and further help to develop pharmacologic strategies targeting cellular methylation machinery in these malignancies.

Carcinogenesis of nasopharyngeal carcinoma:an alternate hypothetical mechanism

Current proposed mechanisms implicate both early and latent Epstein-Barr virus(EBV)infection in the carcinogenic cascade,whereas epidemiological studies have always associated nasopharyngeal carcinoma(NPC)with early childhood EBV infection and with chronic ear,nose,and sinus conditions.Moreover,most patients with NPC present with IgA antibody titers to EBV capsid antigen(VCA-lgA),which can precede actual tumor presentation by several years.If early childhood EBV infection indeed constitutes a key event in NPC carcinogenesis,one would have to explain the inability to detect the virus in normal nasopharyngeal epithelium of patients at a high risk for EBV infection.It is perhaps possible that EBV resides within the salivary glands,instead of the epithelium,during latency.This claim is indirectly supported by observations that the East Asian phenotype shares the characteristics of an increased susceptibility to NPC and immature salivary gland morphogenesis,the latter of which is influenced by the association of salivary gland morphogenesis with an evolutionary variant of the human ectodysplasin receptor gene(EDAR),EDARV370A.Whether the immature salivary gland represents a more favorable nidus for EBV is uncertain,but in patients with infectious mononucleosis,EBV has been isolated in this anatomical organ.The presence of EBV-induced lymphoepitheliomas in the salivary glands and lungs further addresses the possibility of submucosal spread of the virus.Adding to the fact that the fossa of Rosen Muller contains a transformative zone active only in the first decade of life,one might be tempted to speculate the possibility of an alternative carcinogenic cascade for NPC that is perhaps not dissimilar to the model of human papillomavirus and cervical cancer.

EB病毒相关胃癌组织中病毒基因的表达

背景与目的EB病毒(Epstein-Barrvirus,EBV)与多种恶性肿瘤的发生有关,在鼻咽癌及淋巴瘤等组织中EBV的存在形式和表达已有报道,研究表明不同肿瘤组织中EBV的存在形式和表达不同,在胃癌组织中EBV某些基因尤其是裂解性基因的表达情况报道较少。为明确胃癌组织中EBV潜伏性基因和裂解性基因的表达情况,本研究从mRNA水平检测胃癌组织中EBV潜伏感染和裂解感染相关基因的表达,从分子水平探讨EBV编码基因与胃癌发生发展的关系。方法应用PCR-Southern杂交检测185例胃癌及其相应癌旁组织中特异性EBVDNA片段,进一步用原位杂交(ISH)技术检测PCR阳性标本EBV编码小RNA1(EBER1)的表达,癌细胞EBER1阳性者确定为EBV相关胃癌(EBV-associatedgastriccarcinoma,EBVaGC)。采用RT-PCR和Southern杂交技术检测EBVaGCs组织中EBV核抗原(EBNAs)基因转录启动子(Qp、Cp和Wp)、潜伏性基因(EBNA1、EBNA2基因,潜伏膜蛋白LMP1、LMP2A和LMP2B基因)和裂解性基因(即刻早期基因BZLF1和BRLF1,早期基因BARF1和BHRF1,晚期基因BcLF1和BLLF1)的表达。结果185例胃癌标本EBV阳性率为7.03%(13/185),癌旁组织均为阴性。13例EBVaGCs组织中均检测到启动子QpmRNA,而Wp和CpmRNA则为阴性。潜伏性基因中EBNA1mRNA均阳性(13/13),而EBNA2。

EBV相关性胃癌中EB病毒基因表达研究进展

EB病毒(Epstein-Barr virus,EBV)是胃癌发生的生物学病因之一,EBV相关性胃癌(EBV associated gastric carcinoma,EBVaGC)具有独特的临床病理学特征,其预后相对较好,因此EBV导致胃癌的机制研究也备受关注。近年来,随着分子生物学技术的发展,EBVaGC组织中EBV病毒基因表达的研究逐渐增多,为EBVaGC的诊断、治疗和预防提供了一定的理论依据。本文就EBVaGC组织中EBV病毒基因的表达进行综述。

胃癌组织中EB病毒的检测及其增殖期基因的表达

目的 :探讨EB病毒 (Epstein Barrvirus ,EBV)感染与胃癌发生的关系及其增殖期基因在EBV阳性胃癌发生中的作用。方法 :应用聚合酶链反应 (PCR) Southern杂交检测 185例胃癌组织和相应癌旁组织中特异性EBVDNA片段 ,PCR阳性标本用原位杂交 (ISH)技术检测石蜡切片组织中EBV编码小RNA 1(EBER1)的表达 ,以确定EBV阳性胃癌。再应用RT PCR和Southern杂交技术检测EBV增殖期基因 (即刻早期基因BZLF1、BRLF1,早期基因BARF1、BHRF1,晚期基因BcLF1、BLLF1)的表达。结果 :13例胃癌组织EBV阳性 (7.0 3% ) ,癌旁组织未检测到EBV感染 ,胃癌和癌旁组织中EBV阳性率有显著性差异 (χ2 =11.0 76 9,P =0 .0 0 0 9)。EBV阳性和阴性胃癌在年龄、病理类型、临床分期、淋巴结转移和发生部位的差别均无显著性 (P =0 .973,0 .14 1,0 .2 5 9,0 .5 86 ,0 .0 6 2 ) ,但性别之间的差异有显著性 ,男性EBV阳性率高于女性 (χ2 =5 .2 317,P =0 .0 2 1)。增殖期基因中即刻早期基因BZLF1有 6例表达阳性 ,而BRLF1均为阴性 ;早期基因中有 6例BARF1表达阳性 ,2例BHRF1表达阳性 ;晚期基因BcLF1有 7例表达阳性 ,而BLLF1均为阴性。结论 :EBV感染与胃癌的发生有一定的相关性 ,部分EBV阳性胃癌组织中存在EBV增殖性感染 ,早期基因BARF1和BHRF1在EBV阳?

胃癌组织中c-Met蛋白过表达与EBV的相关性

目的:研究EBV相关胃癌(EBV associated gastric carcinomas,EBVaGC)和EBV阴性胃癌(EBV negative gastric carcinomas,EBVnGC)组织中c-Met基因的扩增及表达,探讨c-Met基因扩增和表达与EBV感染的相关性以及二者在胃癌发生发展中的作用. 方法:应用半定量多聚酶链反应(PCR)检测EBVaGC 13 例和EBVnGC 45例组织中c-Met基因的扩增,免疫组化抗原热修复技术检测c-Met蛋白表达. 结果:EBVaGC和EBVnGC组织中均检测到c-Met基因扩增,EBVaGC组织与EBVnGC组织间c-Met基因的扩增水平无显著性差异.EBVaGC癌组织c-Met基因过度扩增率为53.8%(7/13),EBVnGC癌组织c-Met基因过度扩增率为44.4%(20/45),两组之间无差异. EBVaGC和EBVnGC癌组织中c-Met蛋白阳性率分别为76.9%(10/13)和64.4%(29/45),两组之间无显著性差并.EBVaGC和EBVnGC癌组织中c-Met蛋白过表达率分别为69.2%(9/13)和37.8%(17/45),统计学分析表明EBVaGC癌组织中c-Met蛋白的过表达高于EBVnGC 组,两组之间有差异(X2=4.0 345,P=0.0 446). EBVaGC和EBVnGC癌组织中c-Met基因的表达和扩增与肿瘤大小、肿瘤部位、淋巴结转移、分化程度以及临床分期等均无相关性. 结论:胃癌组织中均存在c-Met基因的扩增,EBVaGC 与EBVnGC组织中c-Met基因扩增水平和c-Met蛋白阳性率无明显差异,但EBVaGC癌组织中c-Met蛋白的过表达率高于EBVnGC组.

新城疫病毒HN基因重组体对人胃癌细胞BGC-823凋亡作用机制研究

目的本实验研究旨在探讨含新城疫病毒HN基因的重组质粒对人胃癌细胞BGC-823凋亡的联合作用机制。方法将含有HN基因的重组质粒pIRVP3IL-18HN经脂质体介导转染人胃癌细胞BGC-823,通过MTT方法检测细胞活力;电镜下观察细胞形态;罗丹明123和DCFA染色测定线粒体跨膜电位(△Ψ)和活性氧(ROS)水平变化;底物染色反应检测Caspase-3活性。结果重组质粒pIRVP3IL-18HN转染人胃癌细胞BGC-823后,MTT法结果显示致肿瘤细胞死亡率升高,细胞活力下降;电镜观察肿瘤细胞呈现明显凋亡状态;与阴性空白质粒对照显示,线粒体△Ψ下降,ROS水平升高;Caspase-3活性被激活。结论含新城疫病毒HN基因的重组质粒可以诱导人胃癌细胞BGC-823进入特定的凋亡程序,从而导致人胃癌细胞BGC-823的凋亡。

lncRNA HOTAIR 和H19 SNPs与胃癌及EB病毒相关胃癌遗传易感性的关系

目的:探讨长链非编码RNA(lncRNA)H19及HOTAIR基因多态性与胃癌和EB病毒相关胃癌(EBVaGC)易感性的关系。方法:研究对象选择EB病毒阴性胃癌(EBVnGC)组织65例、EBVaGC组织50例及115例健康人外周血标本,并从中提取其DNA备用。选择H19 rs3024270和rs3741219,以及HOTAIR rs4759314和rs874945共4个基因多态性位点,利用Taq-Man MGB等位基因分型试剂盒对各单核苷酸多态性(SNP)位点基因进行分型,统计分析实验结果。结果:H19及HOTAIR的SNPs在全部标本中均符合Hardy-Weinberg平衡。(1)H19 rs3024270位点的SNP在胃癌组与对照组中的差异有统计学意义(P<0.05);其中G等位基因为保护基因,个体携带G等位基因可显著降低罹患胃癌的风险(P<0.01);(2)HOTAIR rs4759314位点在胃癌组与对照组中基因型和等位基因分布频率均有显著差异(P<0.05);基因型为GG的人群,胃癌的发病风险显著增加(P<0.05);且胃癌的风险基因可能是G等位基因,携带G等位基因人群罹患胃癌的风险显著增加(P<0.05);(3)H19 rs3741219及HOTAIR rs874945位点的各基因型及等位基因频率在两组间无显著差异(P>0.05);(4)HOTAIR rs4759314位点G等位基因在EBVaGC组的分布高于EBVnGC组,而EBVaGC和EBVnGC组间其他SNPs的分布差异均无统计学意义(P>0.05)。结论:H19 rs3024270和HOTAIR rs4759314位点的SNPs与胃癌的发病风险有关,但与EBVaGC的发病风险之间未观察到明确的关联性。

EB病毒相关胃癌与mdm2,p53及p21基因异常的研究

目的探讨p53基因突变以及mdm2,p53和p21蛋白表达异常在EBV相关胃癌(EBVaGC)发生发展中的作用。方法应用免疫组化技术检测13例EBVaGC、45例临床病理资料与之匹配的EBV阴性胃癌(EBVnGC)组织中mdm2,p53和p21蛋白的表达;PCR-SSCP银染技术结合DNA序列分析检测p53基因exon5￣8突变;RT-PCR检测EBV相关基因的表达。结果EBVaGC组与EBVnGC组相比,两组间mdm2,p53和p21蛋白的阳性检出率差异无统计学意义(P=0.8300;P=0.7912;P=0.3531),但EBVaGC组p53蛋白过表达率(15.38%)明显低于EBVnGC组(57.78%),两组间差异有统计学意义(P=0.0085)。mdm2蛋白阳性表达与p53蛋白过表达呈显著正相关(r=0.4391,P=0.0008);p21与p53蛋白共同表达率较高,但两者无显著相关性(r=0.2025,P=0.2501)。2例EBVnGC检测到p53基因突变,突变均位于exon5,13例EBVaGC和58例相应癌旁组织均未检测到p53基因突变。13例EBVaGC核抗原基因EBNA1均为阳性,潜伏膜蛋白基因LMP1均为阴性,即刻早期基因BZLF1,早期基因BARF1和BHRF1阳性率分别为46.15%(6/13),46.15%(6/13)和15.38%(2/13),三者与EBVaGC组织中mdm2,p21和p53蛋白的表达均无显著相关性(P>0.05)。结论EBV感染以及mdm2,p53和p21蛋白表达异常与胃癌发生有关;p53基因突变可能并非胃癌组织中p53蛋白异常累积的主要原因;胃癌组织中EBV感染与p53蛋白的异常表达有关,而与mdm2和p21蛋白的异常表达以及p53基因突变无显著相关性。

潜伏膜蛋白1基因异质性及上皮致瘤性的研究进展

潜伏膜蛋白1(latent membrane protein 1,LMP1)为EB病毒(Epstein-Barr virus,EBV)编码的膜蛋白,在鼻咽癌(nasopharyngeal carcinoma,NPC)和EBV相关胃癌(EBV associated gastric cancer,EBVaGC)等上皮恶性肿瘤中均有表达。作为肿瘤坏死因子(tumor necrosis factor,TNF)受体家族的一员和CD40的组成性活性模拟物,LMP1参与了多种诱导上皮细胞形态和表型改变的信号通路,在啮齿动物成纤维细胞中显现出强大的致癌特性。此外,LMP1是EBV基因组中异质性最高的基因之一。研究LMP1的异质性与其致癌特性有助于发现EBV高危病毒株并为疾病的防治提供新途径。文章就LMP1的异质性及其在上皮恶性肿瘤中的作用两方面的研究进展展开综述。