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 meta lloproteinase-2 (MMP-2) expression in response to insulin like growth facto r-1 (IGF-1) in a H-ras transformed cell line, C3, which is capable of metas tasis formation. These changes in MMP-2 expression in response to IGF-1 tre atment did not occur in either non-transformed parental 10 T1/2 cells or in H-ras transformed cells (NR3 cells) which are capable of benign tumour for mation. IGF-1 treatment of C3 cells resulted in increased expression of MMP -2 gelatinolytic activity and increased expression of MMP-2 mRNA levels. Th e IGF-1 mediated alterations in MMP-2 mRNA levels were dependent upon de no vo protein synthesis and independent of transcriptional events, but depende nt upon post-transcriptional regulatory events. Most notably, IGF-1 can reg ulate MMP-2 mRNA expression in C3 cells through a mechanism involving MMP-2 message stabilization. This study demonstrates aspects of the temporal reg ulatory mechanisms of MMP-2 expression in response to insulin-like growth f actor-1 in a H-ras transformed fibrosarcoma cell line capable of metastasis formation and thereby, provides further insight into the altered growth re gulatory program associated with H-ras mediated cellular transformation and malignant progression.