Integration of the BALB/c ecotropic provirus into the colony-stimulating factor-1 growth factor locus in a myc retrovirus-induced murine monocyte tumor.
The development of tumors is thought to be a multistage process that requires an unknown number of genetic or epigenetic changes in a single cell. We previously described a murine monocyte tumor which was induced by a helper-free c-myc retrovirus and which also contained a DNA rearrangement at the colony-stimulating factor-1 (CSF-1) locus. The CSF-1 gene rearrangement gave rise to high levels of growth factor production and autocrine growth, implicating this secondary event in tumorigenesis. This CSF-1 gene rearrangement was found to be the result of integration of the BALB/c ecotropic retrovirus. Restriction enzyme mapping and DNA sequence analysis demonstrated that the novel provirus is identical to the BALB/c endogenous ecotropic provirus, indicating that infection was probably not due to the creation of a recombinant virus in vivo. The proviral integration site was mapped 3 kilobases 5' of the CSF-1 promoter and in an opposite transcriptional orientation, indicating that activation of CSF-1 expression was the result of the presence of the retroviral enhancer element.
Baumbach
W R
WR
Department of Molecular Biology, Princeton University, New Jersey 08544.
Colston
E M
EM
Cole
M D
MD
D000818:Animals; D003001:Cloning, Molecular; D003115:Colony-Stimulating Factors / Q000096:biosynthesis / Q000235:genetics*; D004279:DNA, Viral / Q000032:analysis; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D051379:Mice; D009000:Monocytes; D009693:Nucleic Acid Hybridization; D011401:Promoter Regions, Genetic; D011533:Proviruses / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics; D011995:Recombination, Genetic; D012190:Retroviridae / Q000235:genetics*; D014412:Tumor Virus Infections / Q000209:etiology / Q000235:genetics*
D003115:Colony-Stimulating Factors; D004279:DNA, Viral; D012333:RNA, Messenger; D012367:RNA, Viral