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Identification of cooperating oncogenes in E mu-myc transgenic mice by provirus tagging
M van Lohuizen1, S Verbeek, B Scheijen
1Division of Molecular Genetics, The Netherlands Cancer Institute, Amsterdam.
Cell
|May 31, 1991
Summary
Moloney murine leukemia virus (Mo-MLV) infection accelerates B cell lymphomagenesis in E mu-myc mice. Provirus tagging identified four cooperating oncogenes: pim-1, bmi-1, pal-1, and bla-1.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- E mu-myc transgenic mice are models for B cell lymphomagenesis.
- Moloney murine leukemia virus (Mo-MLV) infection accelerates tumor development in these mice.
- Identifying cooperating genes is crucial for understanding B cell transformation.
Purpose of the Study:
- To identify genes cooperating with the E mu-myc transgene in B cell transformation using provirus tagging.
- To characterize novel proviral insertion sites and their encoded proteins.
Main Methods:
- Provirus tagging in E mu-myc transgenic mice infected with Mo-MLV.
- Analysis of proviral insertion sites in pre-B cell lymphomas.
- Bioinformatic analysis of the bmi-1 gene and its protein product.
Main Results:
- Four common proviral insertion loci (pim-1, bmi-1, pal-1, bla-1) were identified in 35%, 35%, 28%, and 14% of tumors, respectively.
- bmi-1, pal-1, and bla-1 represent novel common proviral insertion sites.
- The bmi-1 gene encodes a conserved nuclear protein with transcriptional regulator motifs, including a zinc finger.
Conclusions:
- Provirus tagging is effective for identifying cooperating oncogenes in lymphomagenesis.
- The identified loci, particularly bmi-1, pal-1, and bla-1, are significant in B cell transformation.
- Further research is needed to assign genes to pal-1 and bla-1 and to elucidate their roles.
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