HIGH-LEVELS OF EXPRESSION AND NUCLEAR-LOCALIZATION OF INTERLEUKIN-1-BETA CONVERTING-ENZYME (ICE) AND CPP32 IN FAVORABLE HUMAN NEUROBLASTOMAS

Neuroblastomas frequently show spontaneous regression and differentiat ion, which mag at least partly be regulated by signaling through nerve growth factor and its receptors, TRK-A and p75(LNTR). We studied 52 n euroblastic tumors to test whether the cell death-related proteases, i nterleukin-1 beta converting enzyme (ICE), CPP32, and Ich-1, were invo lved in the regression of the tumors. High levels of expression of ICE and CPP32 were significantly correlated with a high level of TRK-A ex pression, single copy of N-myc, younger age, lower stages, and better prognosis, The immunohistochemical studies and Western analyses as wel l as the terminal dUTP-biotin nick end labeling (TUNEL) method reveale d that both ICE and CPP32 were translocated from the cytoplasm into th e nuclei in regressing, apoptotic tumor cells, Our results suggest tha t ICE and CPP32 cysteine proteases may play an important role in regul ating the apoptotic process of the favorable neuroblastomas.