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...
Main Authors: | , , , , , , , , , , , |
---|---|
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 |
_version_ | 1819058000985325568 |
---|---|
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. |
first_indexed | 2024-12-21T13:48:15Z |
format | Article |
id | doaj.art-59fbb30bc5034417a9a1b3c18c1b0f2f |
institution | Directory Open Access Journal |
issn | 1476-5586 1522-8002 |
language | English |
last_indexed | 2024-12-21T13:48:15Z |
publishDate | 2000-05-01 |
publisher | Elsevier |
record_format | Article |
series | Neoplasia: An International Journal for Oncology Research |
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 |
work_keys_str_mv | AT junchen downregulationofsurvivinbyantisenseoligonucleotidesincreasesapoptosisinhibitscytokinesisandanchorageindependentgrowth AT weiwu downregulationofsurvivinbyantisenseoligonucleotidesincreasesapoptosisinhibitscytokinesisandanchorageindependentgrowth AT stephenktahir downregulationofsurvivinbyantisenseoligonucleotidesincreasesapoptosisinhibitscytokinesisandanchorageindependentgrowth AT paulekroeger downregulationofsurvivinbyantisenseoligonucleotidesincreasesapoptosisinhibitscytokinesisandanchorageindependentgrowth AT saulhrosenberg downregulationofsurvivinbyantisenseoligonucleotidesincreasesapoptosisinhibitscytokinesisandanchorageindependentgrowth AT lexmcowsert downregulationofsurvivinbyantisenseoligonucleotidesincreasesapoptosisinhibitscytokinesisandanchorageindependentgrowth AT frankbennett downregulationofsurvivinbyantisenseoligonucleotidesincreasesapoptosisinhibitscytokinesisandanchorageindependentgrowth AT stanislawkrajewski downregulationofsurvivinbyantisenseoligonucleotidesincreasesapoptosisinhibitscytokinesisandanchorageindependentgrowth AT marylakrajewska downregulationofsurvivinbyantisenseoligonucleotidesincreasesapoptosisinhibitscytokinesisandanchorageindependentgrowth AT katewelsh downregulationofsurvivinbyantisenseoligonucleotidesincreasesapoptosisinhibitscytokinesisandanchorageindependentgrowth AT johncreed downregulationofsurvivinbyantisenseoligonucleotidesincreasesapoptosisinhibitscytokinesisandanchorageindependentgrowth AT shichungng downregulationofsurvivinbyantisenseoligonucleotidesincreasesapoptosisinhibitscytokinesisandanchorageindependentgrowth |