Related Experiment Video

Updated: Jul 28, 2026

Defining Gene Functions in Tumorigenesis by Ex vivo Ablation of Floxed Alleles in Malignant Peripheral Nerve Sheath Tumor Cells
09:37

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

Published on: August 25, 2021

p53 cellular localization and function in neuroblastoma: evidence for defective G(1) arrest despite WAF1 induction in

D A Tweddle1, A J Malcolm, M Cole

  • 1Cancer Research Unit, The Medical School, University of Newcastle, Newcastle-upon-Tyne, United Kingdom. d.a.tweedle@newcastle.ac.uk

The American Journal of Pathology
|June 8, 2001
PubMed

Insights

Neuroblastoma cells with MYCN amplification show impaired cell cycle arrest after irradiation, despite functional p53. This suggests MYCN amplification disrupts p53

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Neuroblastoma is a pediatric cancer with complex genetic alterations.
  • The p53 tumor suppressor protein plays a critical role in cellular response to DNA damage.
  • Understanding p53 function in neuroblastoma is crucial for developing targeted therapies.

Purpose of the Study:

  • To investigate if p53 accumulation in neuroblastoma, without mutation, leads to functional inactivation.
  • To examine the impact of p53 functional integrity on downstream mediators in neuroblastoma.
  • To determine the role of MYCN amplification in p53-mediated responses.

Main Methods:

  • Irradiation of 6 neuroblastoma cell lines and 3 primary tumors.
  • Analysis of p53 expression, localization, and transcriptional function.
  • Assessment of cell cycle arrest and apoptosis induction.
  • p53 sequencing to identify mutations and MYCN amplification status.

Main Results:

  • Wild-type p53 was confirmed in all tested neuroblastoma cell lines and tumors.
  • p53 localized to the nucleus and upregulated target genes (WAF1, MDM2) in proliferating neuroblastoma.
  • Irradiation induced G1 cell cycle arrest in cell lines without MYCN amplification but not in those with MYCN amplification, despite WAF1 induction.

Conclusions:

  • p53 exhibits intact transcriptional activity in proliferating neuroblastoma.
  • MYCN amplification appears to interfere with p53-mediated G1 cell cycle arrest.
  • MYCN amplification may alter downstream effectors of p53 signaling in neuroblastoma.

More Related Videos

Genetic Profiling and Genome-Scale Dropout Screening to Identify Therapeutic Targets in Mouse Models of Malignant Peripheral Nerve Sheath Tumor09:33

Genetic Profiling and Genome-Scale Dropout Screening to Identify Therapeutic Targets in Mouse Models of Malignant Peripheral Nerve Sheath Tumor

Published on: August 25, 2023

Identifying, Diagnosing, and Grading Malignant Peripheral Nerve Sheath Tumors in Genetically Engineered Mouse Models08:57

Identifying, Diagnosing, and Grading Malignant Peripheral Nerve Sheath Tumors in Genetically Engineered Mouse Models

Published on: May 17, 2024

Related Concept Videos

Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
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...
DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...