bmi-1 transgene induces lymphomas and collaborates with myc in tumorigenesis.
The bmi-1 gene was discovered as a frequent target of Moloney virus insertion in virally accelerated B-lymphoid tumors of E mu-myc transgenic mice and hence is thought to collaborate with the myc gene in lymphomagenesis, but its oncogenic potential has not previously been tested directly. To determine whether bmi-1 overexpression can contribute to hematopoietic neoplasia in vivo, strains of transgenic mice were generated in which bmi-1 expression was directed to the lymphoid compartment by a coupled immunoglobulin heavy chain enhancer (E mu). Although the E mu-bmi-1 transgene was expressed in both B and T cells, lymphoid development was not perturbed. Nevertheless, 14% of the mice in the strain with highest expression have developed lymphoma. Unexpectedly, most tumors were of the T-cell lineage, although one case of B lymphoma was observed. Furthermore, cross breeding E mu-bmi-1 and E mu-myc mice established that the bmi-1 transgene markedly accelerated the onset of pre-B and B lymphomas. These results demonstrate directly that bmi-1 can contribute to lymphomagenesis in the T and B cell lineages and collaborate with the myc gene in tumor development.
Haupt
Y
Y
Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia.
Bath
M L
ML
Harris
A W
AW
Adams
J M
JM
D000818:Animals; D016259:Genes, myc; D016393:Lymphoma, B-Cell / Q000209:etiology* / Q000235:genetics; D016399:Lymphoma, T-Cell / Q000209:etiology* / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009687:Nuclear Proteins / Q000235:genetics*; D063150:Polycomb Repressive Complex 1; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D016335:Zinc Fingers
C489421:Bmi1 protein, mouse; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D063150:Polycomb Repressive Complex 1