title: Phorbol ester tumour promoter mediated altered expression and regulation of matrix metalloproteinase-2 in a H-ras transformed cell line capable of benign tumour formation.
abstract: The matrix metalloproteinases (MMPs) are thought to play key roles in tumour formation and malignant progression. The present study demonstrates alterations in the regulation of matrix metalloproteinase-2 (MMP-2) expression in response to the phorbol ester tumour promoter, PMA, in a H-ras transformed cell line, NR3, which is capable of benign tumour formation. PMA treatment of NR3 cells resulted in decreased expression of MMP-2 mRNA levels. Following a lag period, an accompanying change in gelatinolytic activity was also found. These PMA-mediated alterations in MMP-2 mRNA levels were independent of de novo protein synthesis and involved both transcriptional and post-transcriptional events. Most notably, PMA regulates MMP-2 mRNA expression through a mechanism involving message de-stabilization. Additionally, protein kinase C mediated events were found to play a role(s) in the regulation of MMP-2 message expression in NR3 cells. This study demonstrates several novel aspects regarding the regulation of MMP-2 expression in a H-ras transformed cell line and thereby provides further insight into the altered growth regulatory programs associated with H-ras mediated cellular transformation.
authors.affiliation: Department of Laboratory Medicine and Pathobiology, St. Michael's Hospital and the University of Toronto, Ontario, Canada.
authors.forename: O
authors.initials: O
authors.lastname: Yeung
authors.forename: R A
authors.initials: RA
authors.lastname: Hurta
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D002273:Carcinogens; D002461:Cell Line, Transformed; D004586:Electrophoresis; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras / Q000235:genetics*; D015151:Immunoblotting; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D051379:Mice; D009369:Neoplasms / Q000201:enzymology / Q000209:etiology*; D010703:Phorbol Esters; D011485:Protein Binding; D011493:Protein Kinase C / Q000378:metabolism / Q000502:physiology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured
chemical_list: D002273:Carcinogens; D010703:Phorbol Esters; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D011493:Protein Kinase C; D020778:Matrix Metalloproteinase 2; D013755:Tetradecanoylphorbol Acetate