Structural and functional characterization of the mouse c-met proto-oncogene (hepatocyte growth factor receptor) promoter

The c-met gene encoding Hepatocyte Growth Factor Receptor is predominantly expressed in epithelial cell types and overexpressed in a variety of human and mouse neoplastic tissues and cell lines. To understand the molecular mechanisms of the transcriptional regulation of this gene, we have cloned and...

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Bibliographic Details
Published in:Biochimica et biophysica acta 1998-02, Vol.1395 (3), p.252-258
Main Authors: Seol, Dai-Wu, Zarnegar, Reza
Format: Article
Language:English
Subjects:
3T3 Cells
Animals
Base Sequence
c-met
Chloramphenicol O-Acetyltransferase - biosynthesis
HGF
Humans
Mice
Molecular Sequence Data
Promoter
Promoter Regions, Genetic
Proto-Oncogene Proteins c-met - biosynthesis
Proto-Oncogene Proteins c-met - genetics
Proto-Oncogenes
Recombinant Fusion Proteins - biosynthesis
Regulatory Sequences, Nucleic Acid
Sp1
Transcription
Transfection
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Summary:The c-met gene encoding Hepatocyte Growth Factor Receptor is predominantly expressed in epithelial cell types and overexpressed in a variety of human and mouse neoplastic tissues and cell lines. To understand the molecular mechanisms of the transcriptional regulation of this gene, we have cloned and functionally characterized the mouse c-met promoter region. Transient transfection analysis using a series of 5′-end deletion met–CAT chimeric constructs in epithelial (C-33A) and fibroblast (NIH3T3) cell lines demonstrated that the c-met promoter acts in a cell-type specific manner. These experiments also localized functionally important regulatory regions at −1390 to −279, relative to the transcription start site, which exert repressive activity, and at −278 to −77 which exhibit enhancing effects on c-met promoter activity. Further analysis by electrophoretic mobility shift assays using specific competitors and antibodies identified Sp1 protein binding to two cognate response elements at −221 and −124 within the enhancer region. Cotransfection experiments revealed that Sp1 stimulated promoter activity of the met–CAT constructs containing the two Sp1 binding sites. These results demonstrate that Sp1 is actively involved in the transcriptional regulation of the c-met promoter.
ISSN:0167-4781
0006-3002
1879-2634
DOI:10.1016/S0167-4781(97)00202-9