Transcriptional regulation of the hepatocyte growth factor gene by pyrrolidine dithiocarbamate.
Hepatocyte growth factor (HGF) mediates cancer cell invasion and metastasis. This study characterised the down-regulation of HGF expression by pyrrolidine dithiocarbamate (PDTC), which markedly reduced HGF mRNA expression and protein production in MRC-5 cells. Reporter gene studies revealed that PDTC inhibited HGF gene transcription and that the response element is located in the region -75 to +42 bp flanking the transcription initiation site. Electrophoretic mobility shift assay identified three specific protein complexes binding in this region, which were abrogated by exposure of cells to PDTC. PDTC deserves further investigation as a novel therapeutic agent for HGF-driven cancers.
Harrison
Phillip M
PM
Kings College London, Department of Liver Studies and Transplantation, Denmark Hill Campus, Bessemer Road, London SE5 9RS, UK. phillip.harrison@kcl.ac.uk <phillip.harrison@kcl.ac.uk>
Farzaneh
Farzin
F
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001483:Base Sequence; D002460:Cell Line; D024202:Electrophoretic Mobility Shift Assay; D017228:Hepatocyte Growth Factor / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000187:drug effects / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D014176:Protein Biosynthesis / Q000187:drug effects / Q000235:genetics; D011759:Pyrrolidines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D013859:Thiocarbamates / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects*
D000970:Antineoplastic Agents; D009687:Nuclear Proteins; D011759:Pyrrolidines; D012333:RNA, Messenger; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid; D017228:Hepatocyte Growth Factor