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

Survivin (SVV) is a family member of inhibitor of apoptosis proteins (IAPs) and its expression is cell cycle regulated. The gene is mapped to chromoso me 17q25, the region of which is frequently gained in advanced stages of ne uroblastoma (NBL). However, the role of SVV in NBL is poorly understood. He re 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 t hose in adult cancer cell lines. In 34 primary NBLs, high levels of SVV exp ression was significantly associated with age greater than 12 months (two s ample 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 line s, SVV mRNA expression was dramatically down-regulated in CHP134 and IMR32 cells undergoing apoptosis after treatment with all-tr mls retinoic acid (R A) or serum deprivation, It was only moderately decreased in cells (SH-SY5Y and CHP901) undergoing RA-induced differentiation, On the other hand, in p roliferating 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. Furt hermore, transfection of SVV into CHP134 cells induced remarkable inhibitio n of the RA-induced apoptosis, Collectively, our results suggest that high expression of SVV is a strong prognostic indicator for the advanced stage n euroblastomas, and that it could be one of the candidate genes for the 17q gain.