Adenovirus E1A does not induce the Ewing tumor-associated gene fusion EWS-FLI1.
Rearrangement of the EWS gene with FLI1 is thought to occur early in the pathogenesis of Ewing's sarcoma family tumors (EFTs) because the chromosomal aberration is pathognomonic for this disease. Recently, adenovirus (Ad) 5 E1A protein has been reported to induce this gene rearrangement in a variety of cell types. This finding, if generally substantiated, not only suggests an etiological role for viral agents in the generation of oncogenic chromosomal aberrations but would also significantly impact the use of adenoviral vectors for gene therapy. In contrast, we now report on the absence of EWS-FLI1 chimeric products from short- and long-term cultures of stably Ad-transformed cells lines and from transiently E1A-expressing cell lines. In addition, we demonstrate the absence of E1A from EFTs. We conclude that there is no role for Ads in EFT pathogenesis. Consequently, evidence for a viral genesis of tumor-specific gene rearrangements is not available.
Kovar
H
H
Children's Cancer Research Institute, St. Anna Kinderspital, Vienna, Austria. kovar@ccri.univie.ac.at
Fallaux
F J
FJ
Pribill
I
I
Jugovic
D
D
Bartl
S
S
Ambros
P F
PF
Aryee
D N
DN
Wiegant
J C
JC
Hoeben
R C
RC
D017500:Adenovirus E1A Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015152:Blotting, Northern; D015153:Blotting, Western; D001859:Bone Neoplasms / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D002461:Cell Line, Transformed; D018076:DNA, Complementary / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D015321:Gene Rearrangement; D006367:HeLa Cells; D006801:Humans; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000378:metabolism; D010957:Plasmids / Q000235:genetics; D051789:Proto-Oncogene Protein c-fli-1; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D034802:RNA-Binding Protein EWS; D012512:Sarcoma, Ewing / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D017500:Adenovirus E1A Proteins; D018076:DNA, Complementary; D004273:DNA, Neoplasm; C106031:EWS-FLI fusion protein; D015514:Oncogene Proteins, Fusion; D051789:Proto-Oncogene Protein c-fli-1; D012334:RNA, Neoplasm; D034802:RNA-Binding Protein EWS; D014157:Transcription Factors