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Division of Biochemistry, Chiba Cancer Center Research Institute, Chiba 260 [A. N., Y. N., T. H., S. S.]; Department of Surgery, Gunma Children's Medical Center, Gunma 377 [H. I.]; Department of Immunology, Tokyo Metropolitan Institute of Medical Science, Tokyo 113 [K. K.], Japan; Vertex Pharmaceuticals Incorporated, Cambridge, Massachusetts 02139 [M. S-S. S.]; and Division of Biostatistics and Epidemiology, Children's Hospital of Philadelphia, Pennsylvania 19104 [H. Z., A. C.]
Neuroblastomas frequently show spontaneous regression and differentiation, which may at least partly be regulated by signaling through nerve growth factor and its receptors, TRK-A and p75LNTR. We studied 52 neuroblastic tumors to test whether the cell death-related proteases, interleukin-1 ß converting enzyme (ICE), CPP32, and Ich-1, were involved in the regression of the tumors. High levels of expression of ICE and CPP32 were significantly correlated with a high level of TRK-A expression, single copy of N-myc, younger age, lower stages, and better prognosis. The immunohistochemical studies and Western analyses as well as the terminal dUTP-biotin nick end labeling (TUNEL) method revealed that both ICE and CPP32 were translocated from the cytoplasm into the nuclei in regressing, apoptotic tumor cells. Our results suggest that ICE and CPP32 cysteine proteases may play an important role in regulating the apoptotic process of the favorable neuroblastomas.
1 Supported by a grant-in-aid for a New Comprehensive 10-year Strategy for Cancer Control from the Ministry of Health and Welfare, Japan.
2 To whom requests for reprints should be addressed, at Division of Biochemistry, Chiba Cancer Center Research Institute, 666-2 Nitona, Chuoh-ku, Chiba 260, Japan. Phone: 81-43-264-5431; Fax: 81-43-265-4459; E-mail: akiranak@biolab.kazusa.or.jp.
Received 3/ 4/97. Accepted 8/14/97.
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