RESUMO
BACKGROUND: The Epstein-Barr virus (EBV) encodes two anti-apoptotic cellular Bcl2 homologs, BALF1 and BHRF1. BHRF1 has an anti-apoptotic activity but is rarely expressed in nasopharyngeal carcinoma (NPC). However, BALF1 is not yet well characterized. OBJECTIVES: The objective of the study was to characterize BALF1 gene. First, the search of its transcriptional expression in EBV-positive B cell lines, EBV-positive Burkitt's lymphoma's cell lines and nasopharyngeal carcinoma's biopsies. Second, the examination of its anti-apoptotic activity in serum dependent assays. STUDY DESIGN: We first analysed the transcriptional expression of BALF1 by reverse transcriptase DNA polymerase chain reaction (RT-PCR) method. For the analysis of its anti-apoptotic activity, we transfected NIH3T3 cells with pBABE-BALF1 expression plasmid and studied serum dependence of these transfectants. RESULTS: BALF1 expression was detected in the latent stage and increased more significantly during the lytic phase in IgG-treated AKATA and TPA-SB-treated P3HR1-TK negative cell lines. As its expression was not affected by the inhibitor of viral DNA synthesis, this gene does not belong to late gene family. When analysed its transcription in Burkitt's lymphoma (BL)-derived cell lines and NPC biopsies, all BL-derived cell lines and more than 80% of NPC biopsies transcribed this gene. The study of serum dependence of BALF1-transfected NIH3T3 cells showed: with 10% of serum, BALF1 transfectants grew significantly more higher cell density than vector alone transfected NIH3T3 cell lines and with 1% of serum, BALF1 transfectants were capable of growing, but with about 40% reduced rate in comparison with those with 10% serum, while vector alone transfected NIH3T3 cells could not almost grow. CONCLUSION: BALF1 gene was transcribed in EBV-associated tumor cells. BALF1 could render cells to serum independent. These results suggest that BALF1 gene could play its role in EBV oncogenesis.
Assuntos
Linfoma de Burkitt/virologia , Herpesvirus Humano 4/genética , Neoplasias Nasofaríngeas/virologia , Transcrição Gênica , Proteínas Virais/genética , Células 3T3 , Animais , Biópsia , Linfoma de Burkitt/genética , Divisão Celular , Linhagem Celular Tumoral , DNA Complementar/genética , DNA Viral/genética , Herpesvirus Humano 4/crescimento & desenvolvimento , Humanos , Camundongos , Neoplasias Nasofaríngeas/genética , RNA Viral/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , TransfecçãoRESUMO
Cases of nasopharyngeal carcinoma (NPC) from North Africa show an unusual bimodal age distribution. As elsewhere, the tumor is closely associated with the presence of Epstein-Barr virus (EBV). The expression of EBV genes and c-onc genes was studied in biopsy specimens from tumors at different clinical stages from 11 young (10 to 30-year-old) and 11 adult (30 to 65-year-old) patients. It was found that the two age groups do not differ in their pattern of gene expression, that there is a tendency for later stage biopsies to express more viral and c-onc transcripts, and that samples expressing larger numbers of EBV genes also tend to express many different c-onc specificities.
Assuntos
Carcinoma/virologia , Expressão Gênica , Herpesvirus Humano 4/genética , Neoplasias Nasofaríngeas/virologia , Proto-Oncogenes , Adolescente , Adulto , África do Norte , Idoso , Envelhecimento , Animais , Carcinoma/patologia , Linhagem Celular , Criança , Dosagem de Genes , Humanos , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/patologia , Transcrição GênicaRESUMO
The genotypes of Epstein-Barr virus (EBV) were investigated in North African nasopharyngeal carcinoma (NPC) biopsies, nasopharyngeal chronic inflammation (NCI) biopsies, and saliva of healthy individuals from Algeria and Tunisia where there is an intermediate incidence of NPC. The prevalence of A-type virus in NPC, NCI biopsies and saliva of healthy individuals was found in these regions by means of a PCR assay. Restriction enzyme polymorphism analysis by Southern blotting revealed that all North African EBV variants have a conserved restriction site on BamHI W'-I' and XhoI LMP gene. No additional BamHI enzyme site on the BamHI-F fragment was observed; however, the presence of an extra BamHI site on the BamHI-H fragment giving 2 HI and H2 fragment-like EBV M-ABA strains was found. All EBV strains present in NPC or NCI biopsies at all ages were homogeneous in these polymorphisms and no correlation was observed between the EBV genotypes from NPC patients and clinical stages of the cancer. These characteristics revealed a significant difference between the EBV variants common in Chinese NPC and those in North African NPC.
