bmi-1 transgene induces lymphomas and collaborates with myc in tumorigenesis

Oncogene. 1993 Nov;8(11):3161-4.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Genes, myc*
  • Lymphoma, B-Cell / etiology*
  • Lymphoma, B-Cell / genetics
  • Lymphoma, T-Cell / etiology*
  • Lymphoma, T-Cell / genetics
  • Mice
  • Mice, Transgenic
  • Nuclear Proteins / genetics*
  • Polycomb Repressive Complex 1
  • Proto-Oncogene Proteins*
  • Repressor Proteins*
  • Zinc Fingers*

Substances

  • Bmi1 protein, mouse
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • Repressor Proteins
  • Polycomb Repressive Complex 1