Proliferate and survive: cell division cycle and apoptosis in human neuroblastoma.
OBJECTIVE
Neuroblastoma is one of the most frequent childhood cancers and a major cause of death from neoplasias of infancy. Although a wealth of studies on its molecular bases have been carried out, little conclusive information about its origin and evolution is available.


METHODS
Some intriguing findings have correlated neuroblastoma development with aberrations of two pivotal cellular processes generally altered in human cancers, namely cell division cycle and apoptosis. Indeed, it has been reported that neuroblastoma cell lines show accumulation of Id2 protein, a factor which is able to hamper the pRb protein antiproliferative activity.


BACKGROUND
The increased Id2 is due to N-myc gene amplification and overexpression, a phenomenon frequently observed in neuroblastoma and an important independent negative marker. Moreover, neuroblastoma cells are frequently characterized by increased levels of survivin, an inhibitor of the apoptotic response, and by a deficiency of procaspase 8, a key intermediate of the programmed cell death cascade. These two events, probably, make neuroblastomas more resistant to programmed cell death. These recent findings might suggest that neuroblastoma cells have acquired the capability to proliferate easily and die difficultly.


CONCLUSIONS
The mechanistic meaning of these data will be discussed in the present review. Moreover, we will suggest new therapeutic scenarios opened up by the described alterations of cell cycle and apoptosis engines.
Borriello
Adriana
A
Department of Biochemistry and Biophysics F. Cedrangolo, Medical School, Second University of Naples, Italy.
Roberto
Roberta
R
Della Ragione
Fulvio
F
Iolascon
Achille
A
D000818:Animals; D017209:Apoptosis; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000172:deficiency / Q000502:physiology; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000502:physiology; D002455:Cell Division; D002470:Cell Survival; D002648:Child; D002675:Child, Preschool; D002868:Chromosomal Proteins, Non-Histone / Q000502:physiology; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000502:physiology; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000502:physiology; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007223:Infant; D051034:Inhibitor of Apoptosis Proteins; D051797:Inhibitor of Differentiation Protein 2; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000502:physiology; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology*; D016271:Proto-Oncogene Proteins c-myc / Q000502:physiology; D012075:Remission, Spontaneous; D012097:Repressor Proteins; D000077022:Survivin; D014157:Transcription Factors / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
C107489:BIRC5 protein, human; C493956:CDKN1A protein, human; C493957:Cdkn1a protein, mouse; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004268:DNA-Binding Proteins; C497450:ID2 protein, human; C497452:Idb2 protein, mouse; D051034:Inhibitor of Apoptosis Proteins; D051797:Inhibitor of Differentiation Protein 2; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D016271:Proto-Oncogene Proteins c-myc; D012097:Repressor Proteins; D000077022:Survivin; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; C505530:CASP8 protein, human; C506433:CASP9 protein, human; C505526:Casp8 protein, mouse; C506434:Casp9 protein, mouse; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases