Role of survivin, whose gene is mapped to 17q25, in human neuroblastoma and identification of a novel dominant-negative isoform, survivin-beta/2B.
METHODS
We investigated the expression of survivin (SVV) and its isoform (SVV-beta/2B) during different biological properties in neuroblastoma (NBL).


RESULTS
High levels of SVV mRNA expression were significantly associated with advanced stages of NBL, diagnosis at over 1 year of age, low levels of TrkA expression, and sporadic tumors. Expression of a novel isoform, SVV-beta/2B, which had an insertion of 23 amino acids within the unique BIR domain was predominant in some favorable NBLs, while it was low and ubiquitous in most normal and malignant tissues. The SVV expression wasdown-regulated during apoptosis induced by retinoic acid (RA) in CHP134 NBL cells, which was inhibited by forced expression of SVV. In contrast, SVV-beta was constantly expressed during apoptosis. Like SVV,SVV-beta was also highly expressed during G(2)/M in a cell cycle-dependent manner, and was associated with but competed against SVV for binding with polymerized tubulin.


CONCLUSIONS
These data suggest that expression of SVV is a poor prognostic indicator in human NBL, and it promotes growth and survival by regulating the levels of both isoforms.
Islam
A
A
Division of Biochemistry, Chiba Cancer Center Research Institute, Chiba, Japan.
Kageyama
H
H
Hashizume
K
K
Kaneko
Y
Y
Nakagawara
A
A
D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D008870:Microtubules / Q000502:physiology; D009363:Neoplasm Proteins; D009447:Neuroblastoma / Q000235:genetics*; D020033:Protein Isoforms / Q000235:genetics; D011506:Proteins / Q000235:genetics* / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D000077022:Survivin; D014407:Tumor Cells, Cultured
C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D020033:Protein Isoforms; D011506:Proteins; D012333:RNA, Messenger; D000077022:Survivin