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PMID: 9950685 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Novel regulation of type IV collagenase (matrix metalloproteinase-9 and -2) activities by transforming growth factor-beta1 in human prostate cancer cell lines.

Molecular biology of the cell ·Vol. 10 ·No. 2 ·1999-02-00 ·Pages 407-16

Sehgal I, Thompson TC

Abstract

The type IV collagenases/gelatinases matrix metalloproteinase-2 (MMP-2) and MMP-9 play a variety of important roles in both physiological and pathological processes and are regulated by various growth factors, including transforming growth factor-beta1 (TGF-beta1), in several cell types. Previous studies have suggested that cellular control of one or both collagenases can occur through direct transcriptional mechanisms and/or after secretion through proenzyme processing and interactions with metalloproteinase inhibitors. Using human prostate cancer cell lines, we have found that TGF-beta1 induces the MMP-9 proenzyme; however, this induction does not result from direct effects on gene transcription but, instead, through a protein synthesis-requiring process leading to increased MMP-9 mRNA stability. In addition, we have examined levels of TGF-beta1 regulation of MMP-2 in one prostate cancer cell line and found that TGF-beta1 induces higher secreted levels of this collagenase through increased stability of the secreted 72-kDa proenzyme. These results identify two novel nontranscriptional pathways for the cellular regulation of MMP-9 and MMP-2 collagenase gene expression and activities.

MeSH Terms
Collagenases/genetics,metabolism Cycloheximide/pharmacology Dactinomycin/pharmacology Gelatinases/genetics,metabolism Gene Expression Regulation, Enzymologic Gene Expression Regulation, Neoplastic Humans Male Matrix Metalloproteinase 2 Matrix Metalloproteinase 9 Metalloendopeptidases/genetics,metabolism Nucleic Acid Synthesis Inhibitors/pharmacology Prostatic Neoplasms/enzymology,genetics Protein Synthesis Inhibitors/pharmacology RNA Processing, Post-Transcriptional/drug effects RNA, Messenger/genetics,metabolism RNA, Neoplasm/genetics,metabolism Transcriptional Activation/drug effects Transforming Growth Factor beta/pharmacology Tumor Cells, Cultured
Chemicals
Nucleic Acid Synthesis Inhibitors Protein Synthesis Inhibitors RNA, Messenger RNA, Neoplasm Transforming Growth Factor beta Dactinomycin Cycloheximide Collagenases Gelatinases Metalloendopeptidases Matrix Metalloproteinase 2 Matrix Metalloproteinase 9
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Sehgal I
Scott Department of Urology, Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
Thompson T C
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Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1059-1524
Published
1999-02-00
Pages
407-16
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC25177
Subset
IM
Grants
NCI NIH HHS · CA50588 · United States
NCI NIH HHS · F32 CA66323 · United States
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