MoMuLV proviral integrations identified by Sup-F selection in tumors from infected myc/pim bitransgenic mice correlate with activation of the gfi-1 gene.
Infecting mice with a mutant Moloney murine leukemia virus which contains the bacterial suppressor tRNA supF in its LTR allows rapid cloning of proviral integration sites from genomic tumour DNA. In a previous study Emu pim-1/Emu L-myc bitransgenic mice had been inoculated neonatally with MoMuLV supF virus. The retroviral infection led to acceleration of lymphomagenesis indicating the proviral activation of further oncogenes cooperating with myc and pim-1 in tumour development. Using a functional supF screen for analysis of genomic mouse tumour DNA libraries which had been constructed in the phage vector EMBL3A, a common proviral integration site on mouse chromosome 5 was cloned and found to be identical to the proviral integration site evi-5 which has recently been identified in an AKXD T-cell lymphoma and which is located 18 kb upstream of the gfi-1 gene. Tumours bearing evi-5 integrations showed an enhanced gfi-1 expression level suggesting that gfi-1 is the target gene for insertions at the evi-5 locus. Together with three other previously described Moloney integration clusters all responsible for enhanced gfi-1 expression the number of tumours from infected double transgenic Emu L-myc/Emu pim-1 transgenic mice with retrovirally activated gfi-1 added up to 53% underscoring the role of GFI-1 as an effective collaborator for MYC and PIM-1 in the process of lymphomagenesis.
Schmidt
T
T
Institut für Zellbiologie (Tumorforschung), IFZ, Universitätsklinikum Essen, Essen, Germany.
Zörnig
M
M
Beneke
R
R
Möröy
T
T
D000818:Animals; D003001:Cloning, Molecular; D004273:DNA, Neoplasm / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D005814:Genes, Viral; D016259:Genes, myc; D008223:Lymphoma / Q000209:etiology / Q000235:genetics*; D016393:Lymphoma, B-Cell / Q000209:etiology / Q000235:genetics; D016399:Lymphoma, T-Cell / Q000209:etiology / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D008979:Moloney murine leukemia virus / Q000235:genetics*; D009857:Oncogenes; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051573:Proto-Oncogene Proteins c-pim-1; D012333:RNA, Messenger / Q000032:analysis; D012343:RNA, Transfer / Q000235:genetics; D012641:Selection, Genetic; D014157:Transcription Factors; D016662:Virus Integration / Q000235:genetics*
D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; C079873:Gfi1 protein, mouse; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D012343:RNA, Transfer; C496636:Pim1 protein, mouse; D017346:Protein Serine-Threonine Kinases; D051573:Proto-Oncogene Proteins c-pim-1