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High expression of Survivin, mapped to 17q25, is significantly associated with poor prognostic factors and promotes cell survival in human neuroblastoma

Abstract

Survivin (SVV) is a family member of inhibitor of apoptosis proteins (IAPs) and its expression is cell cycle regulated. The gene is mapped to chromosome 17q25, the region of which is frequently gained in advanced stages of neuroblastoma (NBL). However, the role of SVV in NBL is poorly understood. Here we studied the clinical and biological role of SVV in NBL. A 1.9 kb SVV transcript was expressed in all of 9 NBL cell lines at higher levels than those in adult cancer cell lines. In 34 primary NBLs, high levels of SVV expression was significantly associated with age greater than 12 months (two sample t-test: P=0.0003), advanced stages (P=0.0136), sporadic tumors (P=0.0027) and low levels of TrkA expression (P=0.0030). In NBL cell lines, SVV mRNA expression was dramatically down-regulated in CHP134 and IMR32 cells undergoing apoptosis after treatment with all-trans retinoic acid (RA) or serum deprivation. It was only moderately decreased in cells (SH-SY5Y and CHP901) undergoing RA-induced differentiation. On the other hand, in proliferating NBL cells or RA-treated SK-N-AS line which is refractory to RA, the SVV mRNA remained at steady state levels or rather up-regulated. Furthermore, transfection of SVV into CHP134 cells induced remarkable inhibition of the RA-induced apoptosis. Collectively, our results suggest that high expression of SVV is a strong prognostic indicator for the advanced stage neuroblastomas, and that it could be one of the candidate genes for the 17q gain.

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References

  • Adida C, Berrebi D, Peuchmaur M, Reyes-Mugica M and Altieri DC. . 1998b Lancet 351: 882–883.

  • Adida C, Crotty PL, McGrath J, Diebold J and Altieri DC. . 1998a Am. J. Pathol. 152: 43–49.

  • Ambrosini G, Adida C and Altieri DC. . 1997 Nat. Med. 3: 917–921.

  • Ambrosini G, Adida C, Sirugo G and Altieri DC. . 1998 J. Biol. Chem. 18: 11177–11182.

  • Barinaga M. . 1998 Science 280: 32–35.

  • Brodeur GM, Pritchard J, Berthold F, Carlsen NLT, Castel V, Castleberry RP, Bernardi BD, Evans AE, Favrot M, Hedborg F, Kaneko M, Tsuchida Y, Philip T, Ronald B and Voute PA. . 1993 J. Clin. Oncol. 11: 1466–1477.

  • Brown N, Cotterill S, Lastowska M, O'Neill S, Pearson ADJ, Plantaz D, Meddeb M, Danglot G, Brinnkschmidt C, Christiansen H, Laureys G and Speleman F. . 1999 N. Eng. J. Med. 340: 1954–1961.

  • Caron H. . 1995 Med. Pediatr. Oncol. 24: 215–221.

  • Chomczynski P and Sacchi N. . 1987 Anal. Biochem. 162: 156–159.

  • Christiansen H, Schestag J, Christiansen NM, Grzeschik K and Lampert F. . 1992 Genes Chromosom. Cancer 5: 141–149.

  • Hoehner JC, Gestblom C, Olsen L and Pahlman S. . 1997 Br. J. Cancer 75: 1185–1194.

  • Inazawa J, Saito H, Ariyama T, Abe T and Nakamura Y. . 1993 Genomics 17: 153–162.

  • Ioannou PA, Amemiya CT, Garnes J, Kroisel PM, Shizuya H, Chen C, Batzer MA and de Jong PJ. . 1994 Nat. Genet. 6: 84–89.

  • Kaneko M, Nishihira H, Mugishima H, Ohnuma N, Nakada K, Kawa K, Fukuzawa M, Suita S, Sera Y and Tsuchida Y. . 1998 Med. Pediatr. Oncol. 31: 1–7.

  • Kobayashi H, Satake N, Maseki N, Sakashita A and Kaneko Y. . 1996 Brit. J. Haematol. 94: 105–111.

  • Lastowska M, Roberts P, Pearson AD, Lewis I, Wolstenholms J and Bown N. . 1997 Genes Chromosomes Cancer 19: 143–149.

  • Li F, Ambrosini G, Chu EY, Plesica J, Tognin S, Marchisio PC and Altieri DC. . 1998 Nature 396: 580–584.

  • Lu C, Altieri DC and Tanigawa N. . 1998 Cancer Res. 58: 1808–1812.

  • Nakagawara A. . 1998a Med. Pediatr. Oncol. 31: 113–115.

  • Nakagawara A. . 1998b Hum. Cell 3: 115–124.

  • Nakagawara A, Arima-Nakagawara M, Scavarda NJ, Azar CG, Cantor AB and Brodeur GM. . 1993 N. Engl. J. Med. 328: 847–854.

  • Nakagawara A, Nakamura Y, Ikeda H, Hiwasa T, Kuida K, Su A, Zhao H, Cnaan A and Sakiyama S. . 1997 Cancer Res. 57: 4578–4584.

  • Plantaz D, Mohapatra G, Matthay KK, Pellarin M, Seeger RC and Feuerstein BG. . 1997 Am. J. Pathol. 150: 81–89.

  • Reed JC. . 1994 J. Cell Biol. 124: 1–4.

  • Shimada H, Chatten J, Newton Jr WA, Sachs N, Hamoudi AB, Chiba T, Marsden HB and Misugi K. . 1984 J. Natl. Cancer Inst. 73: 405–416.

  • Yang E and Korsmeyer SJ. . 1996 Blood 88: 386–401.

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Acknowledgements

We thank H Zhao and M Takahashi for statistical analysis, and H Nakanishi, T Ozaki, N Koshikawa, Y Nakamura, M Miyauchi and S Sakiyama for their kind consultation and support. This work was supported in part by the Research Grant (9A-1) for Nervous and Mental Disorders from the Ministry of Health and Welfare, a grant-in-aid from the Ministry of Health and Welfare for the Study Group for Treatment of Advanced Neuroblastoma, and a grant-in-aid for Scientific Research (B) from the Ministry of Education, Science, Sports and Culture, Japan. N Takada is an awardee of Research Resident Fellowship from the Foundation for Promotion of Cancer Research in Japan. We also thank the following institutions in Japan for providing surgical samples: Department of Pediatric Surgery, Tohoku University; Department of Pediatric Surgery, Jichi Medical University; Department of Surgery, Kiyose Metropolitan Children's Hospital; Department of Pediatric Surgery, Chiba University School of Medicine; Department of Pediatric Surgery, Niigata University School of Medicine; Division of Pediatric Surgery, Niigata Municipal Hospital; Department of Pediatric Surgery, Osaka City General Medical Center; Department of Pediatric Surgery, Saitama Children's Medical Center; the First Department of Surgery, Hokkaido University School of Medicine; Hyogo Children's Hospital; Department of Pediatrics, Aichi Medical College; Department of Surgery, Ichinomiya City Medical Hospital; Division of Surgery, Gunma Children's Medical Center; Iwaki Kyoritsu Hospital; Departments of Pediatrics and Pediatric Surgery, Kagoshima University School of Medicine; Department of Pediatric Surgery, Ohta General Hospital; Department of Pediatric Surgery, Kimitsu Central Hospital; and Department of Pediatrics, Oita Medical College.

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Islam, A., Kageyama, H., Takada, N. et al. High expression of Survivin, mapped to 17q25, is significantly associated with poor prognostic factors and promotes cell survival in human neuroblastoma. Oncogene 19, 617–623 (2000). https://doi.org/10.1038/sj.onc.1203358

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