Role of survivin, whose gene is mapped to 17q25, in human neuroblastoma and identification of a novel dominant-negative isoform, survivin-beta/2B

Procedure. We investigated the expression of survivin (SVV) and its isoform (SVV-beta /2B) during different biological properties in neuroblastoma (NB L). Results. High levels of SVV mRNA expression were significantly associat ed 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, SV V-beta /2B, which bad an insertion of 23 amino acids within the unique BIR domain was predominant in some favorable NBLs, while it was low and ubiquit ous in most normal and malignant tissues. The SVV expression was-down-regul ated during apoptosis induced by retinoic acid (RA) in CHP134 NBL cells, wh ich was inhibited by forced expression of SVV. In contrast, SVV-beta was co nstantly expressed during apoptosis. Like SVV,SVV-beta was also highly expr essed during G(2)/M in a cell cycle-dependent manner, and was associated wi th but competed against SVV for binding with polymerized tubulin. Conclusio n. 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. (C) 2000 Wiley-Liss, Inc.