Translational augmentation of pro‐matrix metalloproteinase 3 (prostromelysin 1) and tissue inhibitor of metalloproteinases (TIMP)‐1 mRNAs induced by epidermal growth factor in human uterine cervical fibroblasts

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Abstract
The mechanisms by which epidermal growth factor (EGF) enhances the production of pro‐matrix metalloproteinase 3 (proMMP‐3/prostromelysin 1) and tissue inhibitor of metalloproteinases (TIMP)‐1 were investigated using human uterine cervical fibroblasts. The treatment of the cells with EGF for 24 h resulted in about 5–6‐fold increase in the production of proMMP‐3 and TIMP‐1 compared with the untreated control cells. This increase was accompanied by an increase of proMMP‐3 and TIMP‐1 mRNAs. However, an about 3‐ and 2‐fold increase in the production of proMMP‐3 and TIMP‐1, respectively, was observed as early as 1 h after the treatment of the cells with EGF, and it was not accompanied by any apparent increase in proMMP‐3 and TIMP‐1 mRNAs. This early effect of EGF on the enhanced production of proMMP‐3 and TIMP‐1 was not inhibited by actinomycin D, even though actinomycin D inhibited the synthesis of the total RNA in both the EGF‐treated and untreated cells. These results indicate that EGF enhances the apparent production of proMMP‐3 and TIMP‐1 by two mechanisms: one by the accelerated translation of their mRNAs; and the other by the enhanced transcription of their genes. The former event takes place much earlier than the latter.