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PMID: 10845561 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Downregulation of the urokinase-type plasminogen activator receptor through inhibition of translation by antisense oligonucleotide suppresses invasion of human glioblastoma cells.

Clinical & experimental metastasis ·Vol. 17 ·No. 7 ·1999-00-00 ·Pages 617-21

Mohan PM, Lakka SS, Mohanam S, Kin Y, Sawaya R, Kyritsis AP, Nicolson GL, Rao JS

Abstract

We previously showed that downregulation of the urokinase-type plasminogen activator receptor (uPAR) in the SNB19 human glioblastoma cell line by the stable transfection of a plasmid expressing a 300 bp antisense sequence to the 5' end of the uPAR gene produced a decrease in the amount of target mRNA. In a more recent study, we found that adenovirus-mediated transduction (Ad-uPAR) of the same uPAR antisense gene construct in SNB19 cells also downregulated uPAR protein levels. We report here that Ad-uPAR-transfected SNB19 cells produced the same amounts of target uPAR mRNA but significantly less protein by in vitro translation and by in situ [35S] labeling compared to Ad-CMV vector-transfected and mock-transfected cells. This antisense construct also inhibited glioblastoma cell invasion confirming previous results. We conclude that downregulation of uPAR by this antisense gene construct results from inhibition of protein translation.

MeSH Terms

Collagen DNA, Antisense/pharmacology Down-Regulation/drug effects Drug Combinations Glioblastoma/metabolism,pathology Humans Laminin Neoplasm Invasiveness/physiopathology,prevention & control Neoplasm Proteins/biosynthesis,genetics,physiology Protein Biosynthesis/drug effects Proteoglycans RNA, Antisense/biosynthesis,genetics RNA, Messenger/metabolism RNA, Neoplasm/metabolism Receptors, Cell Surface/biosynthesis,genetics,physiology Receptors, Urokinase Plasminogen Activator Transfection Tumor Cells, Cultured

Chemicals

DNA, Antisense Drug Combinations Laminin Neoplasm Proteins PLAUR protein, human Proteoglycans RNA, Antisense RNA, Messenger RNA, Neoplasm Receptors, Cell Surface Receptors, Urokinase Plasminogen Activator matrigel Collagen

Authors & Affiliations

8 authors, click to expand affiliations / ORCID

Mohan P M

Department of Neurosurgery, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.

Lakka S S

Mohanam S

Kin Y

Sawaya R

Kyritsis A P

Nicolson G L

Rao J S

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Article Info

Journal

Clinical & experimental metastasis

Abbr.

Clin Exp Metastasis

ISSN

0262-0898

DOI

10.1023/a:1006779902978

Published

1999-00-00

Pages

617-21

Language

English

Region

Netherlands

NLM ID

8409970

Subset

Grants

NCI NIH HHS · CA-75557 · United States

External Links

PubMed source DOI: 10.1023/a:1006779902978 View journal details

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Downregulation of the urokinase-type plasminogen activator receptor through inhibition of translation by antisense oligonucleotide suppresses invasion of human glioblastoma cells.

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