Activation of collagenase IV gene expression and enzymatic activity by the Moloney murine leukemia virus long terminal repeat.
Moloney murine leukemia virus (Mo-MuLV) is a thymotropic and leukemogenic retrovirus which causes T lymphomas and leukemias, yet does not contain a transforming gene product. Mo-MuLV has been shown to trans-activate cellular genes via a polymerase III-generated transcript, designated let, from the long terminal repeat (LTR). Here we demonstrate that introduction of the Mo-MuLV LTR stably, or transiently, into murine or human cultured cells resulted in an 8- to 15-fold increase in collagenase IV (92-kDa gelatinase, gelatinase B, matrix metalloproteinase-9) gene expression. Collagenase IV protein expression was induced 9-fold by stable integration of MuLV LTR, as measured by immunoblot analysis using an anti-collagenase IV polyclonal antibody. The MuLV LTR coordinately stimulated the proteolytic activity of collagenase IV by 14-fold. The AP-1-binding site in the collagenase IV promoter was required for transactivation by the LTR. Collagenase type IV degrades type IV collagen, a major component of basement membrane, which constitutes the first step of the metastatic cascade. The activation of proteolytic enzymes by the MuLV LTR may thus play a contributory role in the development or spread of virus-induced lymphomas or leukemias.
Faller
D V
DV
Department of Medicine, Boston University School of Medicine, Massachusetts 02118, USA.
Weng
H
H
Choi
S Y
SY
D016475:3T3 Cells; D000818:Animals; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis; D017364:Collagenases / Q000096:biosynthesis* / Q000235:genetics*; D015342:DNA Probes; D015971:Gene Expression Regulation, Enzymologic; D015967:Gene Expression Regulation, Viral; D017930:Genes, Reporter; D006367:HeLa Cells; D006801:Humans; D020780:Matrix Metalloproteinase 9; D051379:Mice; D008979:Moloney murine leukemia virus / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D012091:Repetitive Sequences, Nucleic Acid; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection
D015342:DNA Probes; D011993:Recombinant Fusion Proteins; D015500:Chloramphenicol O-Acetyltransferase; D017364:Collagenases; D020780:Matrix Metalloproteinase 9