Regulation of matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1 in MCF-7 cells: comparison with regulatory mechanisms of pS2 expression

✍ Scribed by Anne Hansen Ree; Gunhild M. Mælandsmo; Øystein Fodstad

• Publisher: Springer
• Year: 1996
• Tongue: English
• Weight: 739 KB
• Volume: 14
• Category: Article
• ISSN: 0262-0898
• DOI: 10.1007/bf00123397

✦ Synopsis

Regulation of two genes involved in tumor invasion, the matrix metalloproteinase (MMP)-I and the tissue inhibitor of MMP (TIMP)-I, by activators of protein kinase C (PKC) or protein kinase A (PKA) was studied in MCF-7 mammary adenocarcinoma cells. The basal mRNA expression was undetectable for MMP-1 and low for TIMP-I. Treatment of MCF-7 cells with the phorboi ester 12-O-tetradecanoylphorboi-13acetate (TPA) (100 nM) was associated with a high expression of MMP-1 mRNA, as well as an induction of the level of TIMP-1 mRNA (5-to 10-fold). In the presence of actinomycin D (AMD, 4.0 ~M), an inhibitor of transcription, these stimulatory effects of TPA were abolished. Similar responses were observed when protein synthesis was inhibited by cydoheximide (CHX, 50 ~M). In the presence of the cyclic AMP (cAMP) analogue N6-benzoyl (N6-Bzl)-cAMP (500 ~M), the MMP-1 mRNA was unaffected and still below the level of detection, whereas a non-significant increase (< 2-fold) in TIMP-1 mRNA was observed. The level of pS2 mRNA, of which the induction by TPA in MCF-7 cells is a primary transcriptional event, was up-regulated (10-to 15-fold) by TPA (100 nM), whereas a much weaker increase (2-to 3-fold) was observed by treatment with N6-Bzl-cAMP (500 ~M). Again, these stimulatory effects were counteracted by AMD (4.0 ~M) and CHX (50 ~M). These data suggest that activation of PKC but not of PKA may induce transcription of MMP-1 and TIMP-1, possibly by the synthesis of transcription factor(s), in transformed cells of epithelial origin.