title: High levels of expression and nuclear localization of interleukin-1 beta converting enzyme (ICE) and CPP32 in favorable human neuroblastomas.
abstract: 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 beta 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.
authors.affiliation: Division of Biochemistry, Chiba Cancer Center Research Institute, Japan. akiranak@biolab.kazusa.or.jp
authors.forename: A
authors.initials: A
authors.lastname: Nakagawara
authors.forename: Y
authors.initials: Y
authors.lastname: Nakamura
authors.forename: H
authors.initials: H
authors.lastname: Ikeda
authors.forename: T
authors.initials: T
authors.lastname: Hiwasa
authors.forename: K
authors.initials: K
authors.lastname: Kuida
authors.forename: M S
authors.initials: MS
authors.lastname: Su
authors.forename: H
authors.initials: H
authors.lastname: Zhao
authors.forename: A
authors.initials: A
authors.lastname: Cnaan
authors.forename: S
authors.initials: S
authors.lastname: Sakiyama
mesh_terms: D000367:Age Factors; D017209:Apoptosis; D001932:Brain Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D020170:Caspase 1; D053143:Caspase 2; D053148:Caspase 3; D020169:Caspases; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D003546:Cysteine Endopeptidases / Q000032:analysis / Q000096:biosynthesis*; D004792:Enzyme Precursors / Q000096:biosynthesis; D018305:Ganglioneuroblastoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D005729:Ganglioneuroma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D016259:Genes, myc; D006801:Humans; D007223:Infant; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D011379:Prognosis; D014176:Protein Biosynthesis; D011506:Proteins / Q000032:analysis; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000096:biosynthesis; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis / Q000096:biosynthesis; D020917:Receptor, trkA; D017475:Receptors, Nerve Growth Factor / Q000032:analysis / Q000096:biosynthesis; D015996:Survival Rate
chemical_list: D004792:Enzyme Precursors; D011506:Proteins; D011518:Proto-Oncogene Proteins; D017475:Receptors, Nerve Growth Factor; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA; C505407:CASP3 protein, human; D053143:Caspase 2; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases; D020170:Caspase 1