Epstein-Barr virus nuclear antigen-1 and Myc cooperate in lymphomagenesis.
The lymphomagenic action of myc genes in conjunction with Epstein-Barr virus nuclear antigen-1 (EBNA-1) have been examined using transgenic mice in several separate tests. Synergy between Myc and EBNA-1 in lymphomagenesis was revealed in a cross breed study where co-expression of transgenic myc and EBNA-1 led to a tumor latency period reduced significantly in some crosses. In the resulting bitransgenic tumors, expression of the Emu-myc genes was not affected by EBNA-1 expression. MoMLV was utilized as a transposon tag to activate cellular oncogenes by infection of EmuEBNA-1 mice. Rearrangement at the c-myc locus in B cell tumors from these mice again suggests a cooperative action between myc and EBNA-1. Tumors arising in EmuEBNA-1 mice typically showed a trisomy of chromosome 15, upon which the c-myc locus resides. Bitransgenic tumors (EBNA-1/c-myc) did not show trisomy 15. This raises the possibility that amplification of c-myc is factorial in the selection of trisomy 15 in these tumors. These data indicate that myc and EBNA-1 act cooperatively and are not redundant in lymphomagenesis. Expression of EBNA-1 by EBV may provide a selection pressure in addition to translocation of the c-myc locus in the genesis of endemic Burkitt's lymphoma (BL).
Drotar
Mark E
ME
Division of Molecular Genetics, Faculty of Biomedical and Life Sciences, University of Glasgow, Glasgow G11 6NU, Scotland, UK.
Silva
Santiago
S
Barone
Enrico
E
Campbell
Donald
D
Tsimbouri
Penelope
P
Jurvansu
Jaana
J
Bhatia
Pardeep
P
Klein
George
G
Wilson
Joanna B
JB
D000818:Animals; D001402:B-Lymphocytes / Q000821:virology; D015139:Blotting, Southern; D015153:Blotting, Western; D002875:Chromosomes / Q000235:genetics; D003433:Crosses, Genetic; D020031:Epstein-Barr Virus Infections / Q000473:pathology / Q000821:virology*; D019309:Epstein-Barr Virus Nuclear Antigens / Q000502:physiology*; D005260:Female; D005784:Gene Amplification; D015321:Gene Rearrangement; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D007621:Karyotyping; D016393:Lymphoma, B-Cell / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D016399:Lymphoma, T-Cell / Q000737:chemistry / Q000473:pathology / Q000821:virology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016271:Proto-Oncogene Proteins c-myc / Q000502:physiology*; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D014178:Translocation, Genetic; D014314:Trisomy
D019309:Epstein-Barr Virus Nuclear Antigens; D016271:Proto-Oncogene Proteins c-myc; D012334:RNA, Neoplasm; C417029:EBV-encoded nuclear antigen 1