Sp1 mediates constitutive and transforming growth factor beta-inducible expression of urokinase type plasminogen activator receptor gene in human monocyte-like U937 cells.
Urokinase type plasminogen activator receptor (uPAR) is known to be involved in conversion of plasminogen into plasmin and its expression can be regulated by a variety of biological agents including transforming growth factor beta (TGF-beta). In the present study, we cloned the promoter region of the human uPAR (huPAR) gene (-653 to +61) and investigated the transcription regulatory mechanism of the expression of the huPAR gene upon treatment with TGF-beta in human monocyte-like U937 cells. By deletion and point mutational analysis of the huPAR gene promoter, it was found that the sequence positioned at -70 is required for both constitutive and TGF-beta-inducible expression of the huPAR gene in U937 cells. Using electrophoretic mobility shift assay, we could observe that Sp1 formed a DNA-protein complex at the -70 sequence. In addition, antisense oligonucleotide against human Sp1 blocked both constitutive and TGF-beta-inducible expression of the luciferase reporter gene driven by the huPAR gene promoter in U937 cells. These results led us to conclude that Sp1 transcription factor mediates constitutive and TGF-beta-inducible expression of the huPAR gene in U937 cells through binding to the sequence located at -70.
Park
I K
IK
Department of Microbiology and Cancer Research Center, Seoul National University College of Medicine, and Clinical Research Institute, Seoul National University Hospital, 28 Yongon-Dong, Chongno-Gu, Seoul, Korea.
Lyu
M A
MA
Yeo
S J
SJ
Han
T H
TH
Kook
Y H
YH
D004586:Electrophoresis; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter; D006801:Humans; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism; D055293:Receptors, Urokinase Plasminogen Activator; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D020298:U937 Cells
D016376:Oligonucleotides, Antisense; C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D016329:Sp1 Transcription Factor; D016212:Transforming Growth Factor beta