Related Experiment Video

Updated: Oct 16, 2026

Mosaic Zebrafish Transgenesis for Functional Genomic Analysis of Candidate Cooperative Genes in Tumor Pathogenesis
09:45

Mosaic Zebrafish Transgenesis for Functional Genomic Analysis of Candidate Cooperative Genes in Tumor Pathogenesis

Published on: March 31, 2015

Caspase 8 is deleted or silenced preferentially in childhood neuroblastomas with amplification of MYCN

T Teitz1, T Wei, M B Valentine

  • 1Department of Tumor Cell Biology, St. Jude Children's Research Hospital, 332 N. Lauderdale, Memphis, Tennessee 38101, USA.

Nature Medicine
|May 10, 2000
PubMed

Insights

The gene for caspase 8 (CASP8) is often inactivated in neuroblastoma, a childhood cancer. This inactivation, linked to MYCN amplification, suggests CASP8 acts as a tumor suppressor.

Area of Science:

  • Molecular biology
  • Cancer research
  • Cellular apoptosis

Background:

  • Caspase 8 (CASP8) is a cysteine protease crucial for apoptosis.
  • Apoptosis regulation is vital in preventing uncontrolled cell proliferation.
  • Neuroblastoma is a childhood cancer of the peripheral nervous system.

Purpose of the Study:

  • To investigate the role of Caspase 8 inactivation in neuroblastoma.
  • To determine the mechanisms of CASP8 gene silencing.
  • To assess the functional consequence of CASP8 loss in neuroblastoma development.

Main Methods:

  • Analysis of CASP8 gene status (methylation, deletion) in neuroblastoma samples.
  • Correlation of CASP8 inactivation with MYCN amplification.
  • Functional assays using caspase 8-null neuroblastoma cells to assess apoptosis resistance and correction.

Main Results:

  • CASP8 gene is frequently inactivated in neuroblastoma.
  • Inactivation occurs via DNA methylation and gene deletion.
  • Complete CASP8 inactivation is strongly associated with MYCN amplification.
  • Caspase 8-null cells exhibit resistance to apoptosis, which is reversible upon re-expression of the enzyme.

Conclusions:

  • Caspase 8 functions as a tumor suppressor in neuroblastoma.
  • CASP8 inactivation, particularly in MYCN-amplified tumors, contributes to neuroblastoma pathogenesis.
  • Targeting apoptosis pathways may offer therapeutic strategies for neuroblastoma.

More Related Videos

Defining Gene Functions in Tumorigenesis by Ex vivo Ablation of Floxed Alleles in Malignant Peripheral Nerve Sheath Tumor Cells09:37

Defining Gene Functions in Tumorigenesis by Ex vivo Ablation of Floxed Alleles in Malignant Peripheral Nerve Sheath Tumor Cells

Published on: August 25, 2021

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Induced Pluripotent Stem Cells01:06

Induced Pluripotent Stem Cells

Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic cells are...
Anaphase Promoting Complex00:50

Anaphase Promoting Complex

The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
Epigenetic Regulation01:46

Epigenetic Regulation

Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.