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Biochim Biophys Acta. 2000 Feb 29;1490(3):302-10.

Sp1 mediates constitutive and transforming growth factor beta-inducible expression of urokinase type plasminogen activator receptor gene in human monocyte-like U937 cells.

Author information

1
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.

Abstract

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.

PMID:
10684975
DOI:
10.1016/s0167-4781(99)00246-8
[Indexed for MEDLINE]

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