| First Author | Seol DW | Year | 1998 |
| Journal | Biochim Biophys Acta | Volume | 1395 |
| Issue | 3 | Pages | 252-8 |
| PubMed ID | 9512656 | Mgi Jnum | J:46109 |
| Mgi Id | MGI:1197142 | Doi | 10.1016/s0167-4781(97)00202-9 |
| Citation | Seol DW, et al. (1998) Structural and functional characterization of the mouse c-met proto-oncogene (hepatocyte growth factor receptor) promoter. Biochim Biophys Acta 1395(3):252-8 |
| abstractText | 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. |
