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Role of SURVIVIN (A Novel Anti-apoptosis Gene) in Regulating Differentiation and Apoptosis of Neuroblastoma. : Ashraful ISLAM^1,2, Naoyuki TAKADA¹, Hajime KAGEYAMA¹, Kouhei HASHIZUME², Akira NAKAGAWARA¹, (¹Division of Biochemistry, Chiba Cancer Center Research Institute, ²Department of Pediatric Surgery, Tokyo University School of Medicine)

The inhibitory molecules of programmed cell death (apoptosis) may regulate cell differentiation and aberrantly promote cell survival in neoplasia. Survivin, a novel apoptosis inhibitor of the IAP gene family, was recently found to be expressed at high levels in several apoptosis-regulated fetal tissues as well as in most human cancers, but not in terminally differentiated normal adult tissues. To elucidate the role of survivin in cancers, we investigated expression of survivin in neuroblastoma (NB) which frequently shows spontaneous regression. Fifteen NB cell lines and 14 primary NBs were used for the analysis. Expression of survivin was examined by RT-PCR (a real-time PCR method) and northern analysis using a survivin-specific single-strand probe. A 1.9 Kb transcript was observed in all NB lines at higher levels than in adult cancers. However, the survivin transcripts were expressed at variable levels in 14 primary tumors of all clinical stages. Interestingly, the expression was undectable in two stage 4S tumors. Expression of survivin was down-regulated in NB cell lines (IMR32, CHP134 and TGW) undergoing apoptosis in the serum-free conditions, The similar phenomenon was observed in several NB cell lines treated with all-trans retinoic acid which induced differentiation. Our present studies suggest that survivin plays an important role in regulating neuronal differentiation and apoptosis of NB.