Down-regulation of Survivin by Antisense Oligonucleotides Increases Apoptosis, Inhibits Cytokinesis and Anchorage-Independent Growth

Survivin, a member of the inhibitor of apoptosis protein (IAP) family, is detected in most common human cancers but not in adjacent normal cells. Previous studies suggest that survivin associates with the mitotic spindle and directly inhibits caspase activity. To further investigate the function of...

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Main Authors: Jun Chen, Wei Wu, Stephen K. Tahir, Paul E. Kroeger, Saul H. Rosenberg, Lex M. Cowsert, Frank Bennett, Stanislaw Krajewski, Maryla Krajewska, Kate Welsh, John C. Reed, Shi-Chung Ng
Format: Article
Language:English
Published: Elsevier 2000-05-01
Series:Neoplasia: An International Journal for Oncology Research
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S1476558600800329
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author Jun Chen
Wei Wu
Stephen K. Tahir
Paul E. Kroeger
Saul H. Rosenberg
Lex M. Cowsert
Frank Bennett
Stanislaw Krajewski
Maryla Krajewska
Kate Welsh
John C. Reed
Shi-Chung Ng
author_facet Jun Chen
Wei Wu
Stephen K. Tahir
Paul E. Kroeger
Saul H. Rosenberg
Lex M. Cowsert
Frank Bennett
Stanislaw Krajewski
Maryla Krajewska
Kate Welsh
John C. Reed
Shi-Chung Ng
author_sort Jun Chen
collection DOAJ
description Survivin, a member of the inhibitor of apoptosis protein (IAP) family, is detected in most common human cancers but not in adjacent normal cells. Previous studies suggest that survivin associates with the mitotic spindle and directly inhibits caspase activity. To further investigate the function of survivin, we used a survivin antisense (AS) oligonucleotide to downregulate survivin expression in normal and cancer cells. We found that inhibition of survivin expression increased apoptosis and polyploidy while decreasing colony formation in soft agar. Immunohistochemistry showed that cells without survivin can initiate the cleavage furrow and contractile ring, but cannot complete cytokinesis, thus resulting in multinucleated cells. These findings indicate that survivin plays important roles in a late stage of cytokinesis, as well as in apoptosis.
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spelling doaj.art-59fbb30bc5034417a9a1b3c18c1b0f2f2022-12-21T19:01:47ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022000-05-012323524110.1038/sj.neo.7900091Down-regulation of Survivin by Antisense Oligonucleotides Increases Apoptosis, Inhibits Cytokinesis and Anchorage-Independent GrowthJun Chen0Wei Wu1Stephen K. Tahir2Paul E. Kroeger3Saul H. Rosenberg4Lex M. Cowsert5Frank Bennett6Stanislaw Krajewski7Maryla Krajewska8Kate Welsh9John C. Reed10Shi-Chung Ng11Cancer Research, Pharmaceutical Product Research Division, Abbott Laboratories, Abbott Park, IL 60064Cancer Research, Pharmaceutical Product Research Division, Abbott Laboratories, Abbott Park, IL 60064Cancer Research, Pharmaceutical Product Research Division, Abbott Laboratories, Abbott Park, IL 60064Cancer Research, Pharmaceutical Product Research Division, Abbott Laboratories, Abbott Park, IL 60064Cancer Research, Pharmaceutical Product Research Division, Abbott Laboratories, Abbott Park, IL 60064SIS Pharmaceuticals, Carlsbad, CA 92008SIS Pharmaceuticals, Carlsbad, CA 92008The Burnham Institute, La Jolla, CA 92037SIS Pharmaceuticals, Carlsbad, CA 92008SIS Pharmaceuticals, Carlsbad, CA 92008The Burnham Institute, La Jolla, CA 92037Cancer Research, Pharmaceutical Product Research Division, Abbott Laboratories, Abbott Park, IL 60064Survivin, a member of the inhibitor of apoptosis protein (IAP) family, is detected in most common human cancers but not in adjacent normal cells. Previous studies suggest that survivin associates with the mitotic spindle and directly inhibits caspase activity. To further investigate the function of survivin, we used a survivin antisense (AS) oligonucleotide to downregulate survivin expression in normal and cancer cells. We found that inhibition of survivin expression increased apoptosis and polyploidy while decreasing colony formation in soft agar. Immunohistochemistry showed that cells without survivin can initiate the cleavage furrow and contractile ring, but cannot complete cytokinesis, thus resulting in multinucleated cells. These findings indicate that survivin plays important roles in a late stage of cytokinesis, as well as in apoptosis.http://www.sciencedirect.com/science/article/pii/S1476558600800329survivinapoptosisantisenseoligonucleotidescytokinesis
spellingShingle Jun Chen
Wei Wu
Stephen K. Tahir
Paul E. Kroeger
Saul H. Rosenberg
Lex M. Cowsert
Frank Bennett
Stanislaw Krajewski
Maryla Krajewska
Kate Welsh
John C. Reed
Shi-Chung Ng
Down-regulation of Survivin by Antisense Oligonucleotides Increases Apoptosis, Inhibits Cytokinesis and Anchorage-Independent Growth
Neoplasia: An International Journal for Oncology Research
survivin
apoptosis
antisense
oligonucleotides
cytokinesis
title Down-regulation of Survivin by Antisense Oligonucleotides Increases Apoptosis, Inhibits Cytokinesis and Anchorage-Independent Growth
title_full Down-regulation of Survivin by Antisense Oligonucleotides Increases Apoptosis, Inhibits Cytokinesis and Anchorage-Independent Growth
title_fullStr Down-regulation of Survivin by Antisense Oligonucleotides Increases Apoptosis, Inhibits Cytokinesis and Anchorage-Independent Growth
title_full_unstemmed Down-regulation of Survivin by Antisense Oligonucleotides Increases Apoptosis, Inhibits Cytokinesis and Anchorage-Independent Growth
title_short Down-regulation of Survivin by Antisense Oligonucleotides Increases Apoptosis, Inhibits Cytokinesis and Anchorage-Independent Growth
title_sort down regulation of survivin by antisense oligonucleotides increases apoptosis inhibits cytokinesis and anchorage independent growth
topic survivin
apoptosis
antisense
oligonucleotides
cytokinesis
url http://www.sciencedirect.com/science/article/pii/S1476558600800329
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