Characterization of pal-1, a common proviral insertion site in murine leukemia virus-induced lymphomas of c-myc and Pim-1 transgenic mice.
Insertional mutagenesis with Moloney murine leukemia virus (MoMLV) in c-myc and Pim-1 transgenic mice permits the identification of oncogenes that collaborate with the transgenes in lymphomagenesis. The recently identified common insertion site pal-1, in MoMLV-induced lymphomas, is located in a region in which several independent integration clusters are found: eis-1, gfi-1, and evi-5. Proviral insertions of MoMLV in the different integration clusters upregulate the transcriptional activity of the Gfi-1 gene, which is located within the pal-1 locus. The eis-1/pal-1/gfi-1/evi-5 locus serves as a target for MoMLV proviral insertions in pre-B-cell lymphomas of Emu-myc transgenic mice (20%) and in T-cell lymphomas of H-2K-myc (75%) and Emu-pim-1 (93%) transgenic mice. Many tumors overexpress both Gfi-1 as well as Myc and Pim gene family members, indicating that Gfi-1 collaborates with Myc and Pim in lymphomagenesis. Proviral integrations in the previously identified insertion site bmi-1 are, however, mutually exclusive with integrations in the eis-1/pal-1/gfi-1/evi-5 locus. This finding suggests that Bmi-1 and Gfi-1 belong to the same complementation group in lymphoid transformation.
Scheijen
B
B
Division of Molecular Genetics, The Netherlands Cancer Institute, Amsterdam.
Jonkers
J
J
Acton
D
D
Berns
A
A
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D018076:DNA, Complementary; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D016393:Lymphoma, B-Cell / Q000378:metabolism*; D016399:Lymphoma, T-Cell / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D008979:Moloney murine leukemia virus / Q000235:genetics* / Q000502:physiology; D005810:Multigene Family; D009687:Nuclear Proteins / Q000235:genetics; D063150:Polycomb Repressive Complex 1; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D051573:Proto-Oncogene Proteins c-pim-1; D011533:Proviruses / Q000235:genetics; D012097:Repressor Proteins; D014157:Transcription Factors; D015854:Up-Regulation; D016662:Virus Integration
C489421:Bmi1 protein, mouse; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C079873:Gfi1 protein, mouse; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D012097:Repressor Proteins; D014157:Transcription Factors; D063150:Polycomb Repressive Complex 1; C496636:Pim1 protein, mouse; D017346:Protein Serine-Threonine Kinases; D051573:Proto-Oncogene Proteins c-pim-1