Predisposition to lymphomagenesis in pim-1 transgenic mice: cooperation with c-myc and N-myc in murine leukemia virus-induced tumors.
Transgenic mice bearing the pim-1 gene supplemented with an upstream immunoglobulin enhancer and a downstream murine leukemia virus long terminal repeat express pim-1 mRNA at high levels in both B and T cells. Between 5% and 10% of the pim-1 transgenic mice develop clonal T cell lymphomas before 7 months of age, whereas none of the age-matched control mice do, providing direct evidence for the oncogenic potential of pim-1. Histological examination and FACS analysis revealed no abnormalities in hematopoietic tissues of disease-free pim-1 transgenic mice. When newborn pim-1 transgenic mice are infected with MuLV, T cell lymphomas develop much faster (latency 7-8 weeks) than in nontransgenic mice (latency 22 weeks). In all these T cell lymphomas either c-myc or N-myc was activated by proviral insertion, suggesting strong cooperation between pim-1 and myc in lymphomagenesis.
van Lohuizen
M
M
Division of Molecular Genetics, Netherlands Cancer Institute, Amsterdam.
Verbeek
S
S
Krimpenfort
P
P
Domen
J
J
Saris
C
C
Radaszkiewicz
T
T
Berns
A
A
D000818:Animals; D015152:Blotting, Northern; D002472:Cell Transformation, Viral; D005786:Gene Expression Regulation; D006412:Hematopoietic Stem Cells / Q000502:physiology; D009052:Leukemia Virus, Murine / Q000235:genetics; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc; D051573:Proto-Oncogene Proteins c-pim-1; D013601:T-Lymphocytes / Q000502:physiology
D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; C496636:Pim1 protein, mouse; D017346:Protein Serine-Threonine Kinases; D051573:Proto-Oncogene Proteins c-pim-1