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PMID: 8985317 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Characterization of pal-1, a common proviral insertion site in murine leukemia virus-induced lymphomas of c-myc and Pim-1 transgenic mice.

Journal of virology ·Vol. 71 ·No. 1 ·1997-01-00 ·Pages 9-16

Scheijen B, Jonkers J, Acton D, Berns A

Abstract

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.

MeSH Terms
Amino Acid Sequence Animals Base Sequence DNA, Complementary DNA-Binding Proteins/genetics Female Lymphoma, B-Cell/metabolism Lymphoma, T-Cell/metabolism Male Mice Mice, Transgenic Molecular Sequence Data Moloney murine leukemia virus/genetics,physiology Multigene Family Nuclear Proteins/genetics Polycomb Repressive Complex 1 Protein Serine-Threonine Kinases Proto-Oncogene Proteins/genetics Proto-Oncogene Proteins c-myc/genetics Proto-Oncogene Proteins c-pim-1 Proviruses/genetics Repressor Proteins Transcription Factors Up-Regulation Virus Integration
Chemicals
Bmi1 protein, mouse DNA, Complementary DNA-Binding Proteins Gfi1 protein, mouse Nuclear Proteins Proto-Oncogene Proteins Proto-Oncogene Proteins c-myc Repressor Proteins Transcription Factors Polycomb Repressive Complex 1 Pim1 protein, mouse Protein Serine-Threonine Kinases Proto-Oncogene Proteins c-pim-1
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Scheijen B
Division of Molecular Genetics, The Netherlands Cancer Institute, Amsterdam.
Jonkers J
Acton D
Berns A
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.71.1.9-16.1997
Published
1997-01-00
Pages
9-16
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC191018
Subset
IM
Databases
GENBANK
U58972, U58973
External Links
PubMed source DOI: 10.1128/JVI.71.1.9-16.1997 PMC Full Text View journal details
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