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.
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.
Hosono
T
T
Department of Biochemistry, Tokyo College of Pharmacy, Hachioji, Japan.
Ito
A
A
Sato
T
T
Nagase
H
H
Mori
Y
Y
D002478:Cells, Cultured; D002584:Cervix Uteri / Q000378:metabolism*; D003609:Dactinomycin / Q000494:pharmacology; D004792:Enzyme Precursors / Q000096:biosynthesis* / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D006023:Glycoproteins / Q000096:biosynthesis*; D006801:Humans; D007700:Kinetics; D008666:Metalloendopeptidases / Q000096:biosynthesis*; D014176:Protein Biosynthesis / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism*; D013997:Time Factors; D019714:Tissue Inhibitor of Metalloproteinases
D004792:Enzyme Precursors; D006023:Glycoproteins; D012333:RNA, Messenger; D019714:Tissue Inhibitor of Metalloproteinases; D003609:Dactinomycin; D004815:Epidermal Growth Factor; D008666:Metalloendopeptidases; C048047:prostromelysin