Induction of metalloproteinase (MMP1) expression by epidermal growth factor (EGF) receptor stimulation and serum deprivation in human breast tumour cells

Abstract

The levels of the matrix metalloproteinase MMP1 mRNA in three breast tumour cell lines with varying numbers of epidermal growth factor (EGF) receptors, MDA-MB-231, T47D and MCF7, were investigated following treatment with EGF or TGF alpha in serum-free medium for up to 24 h. A higher level of MMP1 mRNA was found in both control and treated MDA-MB-231 cells compared with the other two cell lines. A 2-fold increase in MMP1 transcripts was observed in MDA-MB-231 cells following a 30 min treatment with EGF and 2 h with TGF alpha. An increase in MMP1 transcripts following serum deprivation in the absence of growth factor stimulation was also seen. This effect was not evident with the other cell lines. In MDA-MB-231 cells, low concentrations of MMP1 protein were detected in medium from treated cells and was only significantly increased after 24 h but it was inhibited by cycloheximide. The early effect of EGF on MMP1 expression was not inhibited by cycloheximide. Treatment with cycloheximide for longer periods produced increased transcripts of MMP1, TGF alpha and EGF-receptor, suggesting the activation of processes for tissue breakdown and subsequent repair may occur on prolonged inhibition of protein synthesis. These results confirm a relationship between EGF-receptor stimulation and MMP1 expression in some EGF-receptor positive tumour cells, which, in part, occurs at the transcriptional level, and have implications for the invasive progression of EGF-receptor positive tumours particularly in areas of nutritional deprivation.