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 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.
Cancer Research, Pharmaceutical Product Research Division, Abbott Laboratories, Abbott Park, IL 60064, USA.
J
J
Chen
W
W
Wu
S K
SK
Tahir
P E
PE
Kroeger
S H
SH
Rosenberg
L M
LM
Cowsert
F
F
Bennett
S
S
Krajewski
M
M
Krajewska
K
K
Welsh
J C
JC
Reed
S C
SC
Ng
D017209:Apoptosis / Q000187:drug effects*; D002455:Cell Division; D015536:Down-Regulation; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D009369:Neoplasms / Q000473:pathology / Q000628:therapy*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D011506:Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D000077022:Survivin; D014407:Tumor Cells, Cultured
C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D016376:Oligonucleotides, Antisense; D011506:Proteins; D000077022:Survivin