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PMID: 9789069 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Regulation of matrix metalloproteinase-9 and inhibition of tumor invasion by the membrane-anchored glycoprotein RECK.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 95 ·No. 22 ·1998-10-27 ·Pages 13221-6

Takahashi C, Sheng Z, Horan TP, Kitayama H, Maki M, Hitomi K, Kitaura Y, Takai S, Sasahara RM, Horimoto A, Ikawa Y, Ratzkin BJ, Arakawa T, Noda M

Abstract

A human fibroblast cDNA expression library was screened for cDNA clones giving rise to flat colonies when transfected into v-Ki-ras-transformed NIH 3T3 cells. One such gene, RECK, encodes a membrane-anchored glycoprotein of about 110 kDa with multiple epidermal growth factor-like repeats and serine-protease inhibitor-like domains. While RECK mRNA is expressed in various human tissues and untransformed cells, it is undetectable in tumor-derived cell lines and oncogenically transformed cells. Restored expression of RECK in malignant cells resulted in suppression of invasive activity with concomitant decrease in the secretion of matrix metalloproteinase-9 (MMP-9), a key enzyme involved in tumor invasion and metastasis. Moreover, purified RECK protein was found to bind to, and inhibit the proteolytic activity of, MMP-9. Thus, RECK may link oncogenic signals to tumor invasion and metastasis.

MeSH Terms
3T3 Cells Amino Acid Sequence Animals Cell Transformation, Neoplastic Cloning, Molecular Collagenases/biosynthesis,genetics DNA, Complementary GPI-Linked Proteins Gene Expression Regulation, Enzymologic Gene Expression Regulation, Neoplastic Gene Library Genes, ras Humans Lymphatic Metastasis Matrix Metalloproteinase 9 Membrane Glycoproteins/chemistry,genetics,metabolism Mice Mice, Inbred C57BL Mice, Inbred ICR Mice, Nude Molecular Sequence Data Neoplasm Invasiveness/genetics Neoplasm Metastasis Neoplasms, Experimental/genetics,pathology Oncogenes Sequence Alignment Sequence Homology, Amino Acid Transfection
Chemicals
DNA, Complementary GPI-Linked Proteins Membrane Glycoproteins RECK protein, human Reck protein, mouse Collagenases Matrix Metalloproteinase 9
Authors & Affiliations
14 authors, click to expand affiliations / ORCID
Takahashi C
Department of Molecular Oncology, Kyoto University Graduate School of Medicine, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
Sheng Z
Horan T P
Kitayama H
Maki M
Hitomi K
Kitaura Y
Takai S
Sasahara R M
Horimoto A
Ikawa Y
Ratzkin B J
Arakawa T
Noda M
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.95.22.13221
Published
1998-10-27
Pages
13221-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC23764
Subset
IM
Databases
GENBANK
AB006960, D50406
External Links
PubMed source DOI: 10.1073/pnas.95.22.13221 PMC Full Text View journal details
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