Insulin like growth factor-1 selectively regulates the expression of matrix metalloproteinase-2 in malignant H-ras transformed cells.
The present study demonstrates alterations in the regulation of matrix metalloproteinase-2 (MMP-2) expression in response to insulin like growth factor-1 (IGF-1) in a H-ras transformed cell line, C3, which is capable of metastasis formation. These changes in MMP-2 expression in response to IGF-1 treatment did not occur in either non-transformed parental 10 T 1/2 cells or in H-ras transformed cells (NR3 cells) which are capable of benign tumour formation. IGF-1 treatment of C3 cells resulted in increased expression of MMP-2 gelatinolytic activity and increased expression of MMP-2 mRNA levels. The IGF-1 mediated alterations in MMP-2 mRNA levels were dependent upon de novo protein synthesis and independent of transcriptional events, but dependent upon post-transcriptional regulatory events. Most notably, IGF-1 can regulate MMP-2 mRNA expression in C3 cells through a mechanism involving MMP-2 message stabilization. This study demonstrates aspects of the temporal regulatory mechanisms of MMP-2 expression in response to insulin-like growth factor-1 in a H-ras transformed fibrosarcoma cell line capable of metastasis formation and thereby, provides further insight into the altered growth regulatory program associated with H-ras mediated cellular transformation and malignant progression.
Yoon
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Department of Laboratory Medicine and Pathobiology, St. Michael 's Hospital and the University of Toronto, Ontario, Canada.
Hurta
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RA
D000818:Animals; D002461:Cell Line, Transformed; D003513:Cycloheximide / Q000494:pharmacology; D004586:Electrophoresis / Q000379:methods; D005354:Fibrosarcoma / Q000201:enzymology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects* / Q000502:physiology; D011905:Genes, ras; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D020871:RNA Stability; D014407:Tumor Cells, Cultured
D011500:Protein Synthesis Inhibitors; D007334:Insulin-Like Growth Factor I; D003513:Cycloheximide; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9