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Analysis of proviruses integrated in Fli-1 and Evi-1 regions in Cas-Br-E MuLV-induced non-T-, non-B-cell leukemias.

Abstract：

:The DNAs of the Cas-Br-E MuLV-induced leukemias always contain somatically acquired mink cell focus-forming (MCF) recombinant proviruses. MCF recombinants could be involved during leukemogenesis at both preleukemic times and in late-stage tumors. Among the Cas-Br-E-induced non-T-, non-B-cell leukemias, viral integrations were found in the Fli-1 and Evi-1 region in 71% (36 out of 51) and 22% (16 out of 72) of the tumors analyzed, respectively. As an approach to evaluate the contribution of Cas-Br-E MCF recombinant formation in cis-activation of proto-oncogenes, we analyzed the structure of the Fli-1- and Evi-1-associated proviruses by Southern blot hybridization. In Fli-1, we found that the proviruses, ecotropic as well as MCF, are all integrated within a very short DNA region immediately upstream of the initiator ATG, toward the 3' end of a 5' exon (Ben-David, Giddens, Letwin, and Bernstein, 1991, Genes Dev. 5, 908-918). All proviruses are oriented the same way, in the 5' to 3' transcriptional sense. Both provirus types are able to direct the Fli-1 expression to the same extent presumably via a promoter insertion mechanism. Most of the proviruses had no detectable deletion and contained both 5' and 3' LTR sequences with similar U3 sequences. MCF recombinants did not show any selective advantage over ecotropic proviruses for the Fli-1 locus since the frequency of ecotropic to MCF-recombinant virus at the Fli-1 locus was identical to that observed at any other locus. This suggests that the formation of these MCF recombinants is not essential for activation of Fli-1 and that ecotropic Cas-Br-E already possesses the required sequences for full cis-activation of Fli-1. On the other hand, in Evi-1, there is a strict selection for ecotropic proviruses. Presumably, viral genetic elements outside of the U3 region could be critical for the Evi-1 cis-activation.

journal_name

Virology

journal_title

Virology

authors

Bergeron D,Poliquin L,Houde J,Barbeau B,Rassart E

doi

10.1016/0042-6822(92)90241-g

subject

Has Abstract

pub_date

1992-12-01 00:00:00

pages

661-9

issue

eissn

0042-6822

issn

1096-0341

journal_volume

191

pub_type

杂志文章

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Analysis of proviruses integrated in Fli-1 and Evi-1 regions in Cas-Br-E MuLV-induced non-T-, non-B-cell leukemias.