Inhibition of NF-KB-Rel A expression by antisense oligodeoxynucleotides suppresses synthesis of urokinase-type plasminogen activator (uPA) but not its inhibitor PAl-1
Identifieur interne : 004084 ( Main/Exploration ); précédent : 004083; suivant : 004085Inhibition of NF-KB-Rel A expression by antisense oligodeoxynucleotides suppresses synthesis of urokinase-type plasminogen activator (uPA) but not its inhibitor PAl-1
Auteurs : Ute Reuning [Italie] ; Olaf Wilhelm [Italie] ; Tomizo Nishiguchi [Japon] ; Luisa Guerrini [Italie] ; Francesco Blasi [Italie] ; Henner Graeff [Italie] ; Manfred Schmitt [Italie]Source :
- Nucleic Acids Research [ 0305-1048 ] ; 1995.
Abstract
The essential role of uroklnase-type plasminogen activator (uPA) in tumor invasion and metastasis stresses the necessity of a fine-tuned cellular control over its expression. It has been shown that changes in uPA directly correlate with changes in cell invasive ness. We examined the role of Rel-related proteins in uPA synthesis by human ovarian cancer cells by inhibiting their expression using the antisense (AS) oligodeoxynucleotide (ODN) technology. Exposure of OV-MZ-6 cells to 10μM phosphorothioate (PS)-dervatized AS-ODN directed to Rel A led to a maximal 50% decrease of uPA antigen in cell lysates and a 70% reduction in cell culture supematants accompanied by a significant transient decline in uPA mRNA levels. Antisense-PS-ODN directed to NF-kB1 (p50) or c-rel had no effect on uPA protein expression. AS-PS-ODN directed to Rel A also affected the proteotytic capacity of OV-MZ-6 cells reflected by an -70% decrease in the tibrinolytic capacity of the cells within 24 h compared to untreated controls. AS-PS-ODN directed to 1kBα expression increased uPA in cell culture supematants up to 50%. uPA receptor (uPAR) production and synthesis of plasminogen activator inhibitor type-1 (PM-1) were not altered by either AS-PS-ODN applied. Western blot and gel retardation analyses revealed constitutive expression of Relrelated proteins in nuclear protein extracts of OV-MZ-6 cells. Thus these proteins seem to be implicated in uPA regulation and may thereby contribute to tumor spread and metastasis.
Url:
DOI: 10.1093/nar/23.19.3887
Affiliations:
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tumor invasion and metastasis stresses the necessity of a fine-tuned cellular control over its expression. It has been shown that changes in uPA directly correlate with changes in cell invasive ness. We examined the role of Rel-related proteins in uPA synthesis by human ovarian cancer cells by inhibiting their expression using the antisense (AS) oligodeoxynucleotide (ODN) technology. Exposure of OV-MZ-6 cells to 10μM phosphorothioate (PS)-dervatized AS-ODN directed to Rel A led to a maximal 50% decrease of uPA antigen in cell lysates and a 70% reduction in cell culture supematants accompanied by a significant transient decline in uPA mRNA levels. Antisense-PS-ODN directed to NF-kB1 (p50) or c-rel had no effect on uPA protein expression. AS-PS-ODN directed to Rel A also affected the proteotytic capacity of OV-MZ-6 cells reflected by an -70% decrease in the tibrinolytic capacity of the cells within 24 h compared to untreated controls. AS-PS-ODN directed to 1kBα expression increased uPA in cell culture supematants up to 50%. uPA receptor (uPAR) production and synthesis of plasminogen activator inhibitor type-1 (PM-1) were not altered by either AS-PS-ODN applied. Western blot and gel retardation analyses revealed constitutive expression of Relrelated proteins in nuclear protein extracts of OV-MZ-6 cells. Thus these proteins seem to be implicated in uPA regulation and may thereby contribute to tumor spread and metastasis.</div></front></TEI><affiliations><list><country><li>Italie</li><li>Japon</li></country><region><li>Lombardie</li></region><settlement><li>Milan</li></settlement><orgName><li>Université Louis-et-Maximilien de Munich</li></orgName></list><tree><country name="Italie"><region name="Lombardie"><name sortKey="Reuning, Ute" sort="Reuning, Ute" uniqKey="Reuning U" first="Ute" last="Reuning">Ute Reuning</name></region><name sortKey="Blasi, Francesco" sort="Blasi, Francesco" uniqKey="Blasi F" first="Francesco" last="Blasi">Francesco Blasi</name><name sortKey="Blasi, Francesco" sort="Blasi, Francesco" uniqKey="Blasi F" first="Francesco" last="Blasi">Francesco Blasi</name><name sortKey="Graeff, Henner" sort="Graeff, Henner" uniqKey="Graeff H" first="Henner" last="Graeff">Henner Graeff</name><name sortKey="Guerrini, Luisa" sort="Guerrini, Luisa" uniqKey="Guerrini L" first="Luisa" last="Guerrini">Luisa Guerrini</name><name sortKey="Schmitt, Manfred" sort="Schmitt, Manfred" uniqKey="Schmitt M" first="Manfred" last="Schmitt">Manfred Schmitt</name><name sortKey="Wilhelm, Olaf" sort="Wilhelm, Olaf" uniqKey="Wilhelm O" first="Olaf" last="Wilhelm">Olaf Wilhelm</name></country><country name="Japon"><noRegion><name sortKey="Nishiguchi, Tomizo" sort="Nishiguchi, Tomizo" uniqKey="Nishiguchi T" first="Tomizo" last="Nishiguchi">Tomizo Nishiguchi</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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