Tumor progression mediated by two cooperating DNA segments of human cytomegalovirus.
The terminal fragments (EJ and EM) of the XbaI-E transforming segment of human cytomegalovirus can independently induce the tumorigenic conversion of immortalized cells. To study their interaction, Rat-2 cells were transfected singly or with a combination of cloned EJ and EM DNAs. Large transformed foci were induced at a 10-fold higher frequency by EJ plus EM than by either DNA fragment alone. Focus-derived lines transformed by EJ plus EM produced tumors in syngeneic rats at a much faster rate (5 to 7 days) than did cell lines transformed by EJ or EM alone (25 to 35 days). Southern hybridizations showed that EM-homologous DNA was retained, exhibiting a complex pattern of multiple and amplified bands in EJ-plus-EM lines compared to a simple pattern in EM-induced lines. EJ DNA was not detected in the single or double transformants. The levels of p29, a 29-kilodalton transformation-sensitive marker in Rat-2 cells, were decreased 10- to 100-fold in cell lines transformed by EJ or EM fragment alone. Synthesis of p29 was shut off in EJ- plus-EM transformants. These data demonstrate that two unlinked transforming regions of human cytomegalovirus can cooperate to produce an aggressive tumorigenic phenotype.
Jariwalla
R J
RJ
Armand Hammer Cancer Research Center, Linus Pauling Institute of Science and Medicine, Palo Alto, California 94306.
Razzaque
A
A
Lawson
S
S
Rosenthal
L J
LJ
D000818:Animals; D015139:Blotting, Southern; D002471:Cell Transformation, Neoplastic; D002472:Cell Transformation, Viral; D003587:Cytomegalovirus / Q000235:genetics*; D015342:DNA Probes; D004279:DNA, Viral / Q000032:analysis / Q000235:genetics*; D051381:Rats; D015183:Restriction Mapping; D014162:Transfection; D014407:Tumor Cells, Cultured
D015342:DNA Probes; D004279:DNA, Viral