T cell leukemia I oncogene expression depends on the presence of Epstein-Barr virus in the virus-carrying Burkitt lymphoma lines.
We used a modified subtractive suppression hybridization to identify cellular genes that show altered expression in Burkitt lymphomas (BLs) in the presence of Epstein-Barr virus (EBV). Comparison of the gene expression patterns of an EBV-negative clone of the originally EBV-positive BL line Akata, with its Neo(R)-EBV derivative, revealed a significant difference in the expression of the T cell leukemia 1 oncogene (TCL-1). Subsequent expression studies showed that the original EBV-positive Akata line and the EBV-reconstituted derivative expressed high levels of TCL-1, whereas the EBV-negative variant showed only a low level of expression. Two other independently established EBV-positive BLs (Mutu and OMA) that have also thrown off EBV showed a similar decrease in TCL-1 expression after virus loss. Reinfection with Neo(R)-EBV restored the TCL-1 expression levels in the EBV loss variants to as high a level as the originally EBV-positive lines. High-resolution immunostaining showed that TCL-1 was localized in both the cytoplasm and the nucleus. Our findings suggest that high expression of TCL-1 is necessary for the development of the BL phenotype. In view of the fact that germinal center B cells, regarded as the progenitors of BL, do not express TCL-1, we suggest that constitutive expression of this oncogene occurs by genetic or epigenetic changes in the EBV-negative BLs. In the originally EBV-positive BLs, the ability of the virus to switch on TCL-1 expression would obviate this need.
Kiss
Csaba
C
Microbiology and Tumor Biology Center, Karolinska Institute, S-171 77 Stockholm, Sweden. csaba.kiss@mtc.ki.se
Nishikawa
Jun
J
Takada
Kenzo
K
Trivedi
Pankaj
P
Klein
George
G
Szekely
Laszlo
L
D001483:Base Sequence; D002051:Burkitt Lymphoma / Q000235:genetics* / Q000378:metabolism / Q000821:virology*; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D004854:Herpesvirus 4, Human / Q000302:isolation & purification / Q000472:pathogenicity*; D006801:Humans; D008954:Models, Biological; D009857:Oncogenes; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012334:RNA, Neoplasm / Q000235:genetics; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D011518:Proto-Oncogene Proteins; D012334:RNA, Neoplasm; C090851:TCL1A protein, human