Caspase 3 and 8 deficiency in human neuroblastoma

Cancer Genet Cytogenet. 2003 Oct 1;146(1):41-7. doi: 10.1016/s0165-4608(03)00125-0.

Abstract

An altered apoptotic response represents a pivotal feature of cancer and is involved in cancerogenesis and resistance to chemotherapy. So far, however, only a few studies have been devoted to survey caspase content in malignant cell lines and primary tumor specimens. In this report, we investigated the expression of two pivotal caspases, 3 and 8, in 63 neuroblastoma specimens by three complementary techniques (i.e., reverse transcriptase polymerase chain reaction, immunoblotting, and immunohistochemistry). We confirmed the frequent absence of caspase 8 expression. Moreover and most important, we demonstrated, for the first time to our knowledge, that a significant percentage of neuroblastomas lack caspase 3 mRNA and protein. Both caspase alterations do not show any correlation with tumor stage and MYCN status. Immunohistochemistry showed a large number of caspase-negative cell islets also present in positive samples. Our findings suggest that the absence of caspases might play an important role in neuroblastoma development and resistance to apoptosis-based treatments.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Caspase 3
  • Caspase 8
  • Caspase 9
  • Caspases / deficiency*
  • Caspases / genetics
  • Drug Resistance, Neoplasm / genetics
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunoblotting
  • Immunohistochemistry
  • N-Myc Proto-Oncogene Protein
  • Neuroblastoma / drug therapy
  • Neuroblastoma / enzymology*
  • Neuroblastoma / genetics
  • Neuroblastoma / pathology
  • Nuclear Proteins / genetics
  • Oncogene Proteins / genetics
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • MYCN protein, human
  • N-Myc Proto-Oncogene Protein
  • Nuclear Proteins
  • Oncogene Proteins
  • CASP3 protein, human
  • CASP8 protein, human
  • CASP9 protein, human
  • Caspase 3
  • Caspase 8
  • Caspase 9
  • Caspases