Activation of multiple genes by provirus integration in the Mlvi-4 locus in T-cell lymphomas induced by Moloney murine leukemia virus

P. N. Tsichlis, J. S. Lee, S. E. Bear, P. A. Lazo, C. Patriotis, E. Gustafson, S. Shinton, N. A. Jenkins, N. G. Copeland, K. Huebner, C. Croce, G. Levan, C. Hanson

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

Moloney murine leukemia virus-induced rat T-cell lymphomas harbor proviruses integrated near c-myc and near Mlvi-1/Mis-1/Pvt-1, another locus of common integration which maps 270 kilobases 3′ of c-myc. In this report, we present the characterization of a new locus of common integration in Moloney murine leukemia virus-induced T-cell lymphomas (Mlvi-4) which maps 30 kilobases 3′ of c-myc, between c-myc and Mlvi-1. The Mlvi-4 locus, whose chromosomal map location is conserved in rats, mice, and humans, is also the target of chromosomal rearrangements in a variety of animal and human tumors. Evidence presented elsewhere shows that provirus integration in Mlvi-4 enhances the expression of c-myc and Mlvi-1 by m-acting mechanisms operating over long distances of genomic DNA. In this manuscript, we show that provirus integration in the Mlvi-4 locus activates, by promoter insertion, one additional gene which maps immediately 3′ to the cluster of the Mlvi-4 proviruses and which is transcribed in the same orientation as c-myc, giving rise to 3- and 10-kilobase mRNA transcripts. The Mlvi-4 gene is also expressed in normal thymus and spleen at very low levels, giving rise to 3- and 5.5-kik base messages. Although Mlvi-4 is expressed in normal thymus, it is not expressed in Moloney murine leukemia virus-induced T-cell lymphomas corresponding to several stages of T-cell differentiation, but lacking a provirus in this locus. This suggests that Mlvi-4 may be expressed only in a subpopulation of T cells. We conclude that provirus insertion in Mlvi-4 activates c-myc and two additional genes, Mlvi-1 and Mlvi-4, whose expression is restricted to, and may be developmentally regulated in, T cells. Since Mlvi-4 is the target of genetic changes in a great variety of human and animal neoplasms, these results are critical for our understanding of oncogenesis.

Original languageEnglish (US)
Pages (from-to)2236-2244
Number of pages9
JournalJournal of virology
Volume64
Issue number5
DOIs
StatePublished - 1990

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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