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

Autor: 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
Jazyk: angličtina
Rok vydání: 2000
Předmět:
Zdroj: Neoplasia: An International Journal for Oncology Research, Vol 2, Iss 3, Pp 235-241 (2000)
Druh dokumentu: article
ISSN: 1476-5586
1522-8002
DOI: 10.1038/sj.neo.7900091
Popis: 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.
Databáze: Directory of Open Access Journals