Related Experiment Video

Updated: Jun 7, 2025

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

1.7K

Conditional Activation of c-MYC in Distinct Catecholaminergic Cells Drives Development of Neuroblastoma or

Tingting Wang1, Lingling Liu1, Jie Fang2

  • 1Center for Childhood Cancer Research, Hematology, Oncology and BMT, Abigail Wexner Research Institute at Nationwide Children's Hospital, Department of Pediatrics at The Ohio State University, Columbus, Ohio.

Cancer Research
|November 12, 2024
PubMed

Insights

Genetically engineered mouse models (GEMM) were developed to study neuroblastoma. These models, driven by c-MYC, successfully mimicked human disease and responded to targeted therapies.

Area of Science:

  • Oncology
  • Genetics
  • Mouse Models

Background:

  • c-MYC is a key driver in high-risk neuroblastoma.
  • Lack of c-MYC-driven genetically engineered mouse models (GEMM) hinders research into neuroblastoma oncogenesis and therapy development.

Purpose of the Study:

  • To create and characterize c-MYC-driven GEMMs for neuroblastoma research.
  • To investigate the role of c-MYC in different tumor types based on cell-specific induction.
  • To evaluate the efficacy of existing therapies in these novel GEMMs.

Main Methods:

  • Conditional c-MYC induction using Cre recombinase under specific neuronal promoters (tyrosine hydroxylase and dopamine β-hydroxylase).
  • Characterization of resulting tumors for pathologic and genetic features compared to human neuroblastoma.
  • Testing response to anti-GD2 immunotherapy and difluoromethylornithine (DFMO).

Main Results:

  • Induction via tyrosine hydroxylase promoter led to pancreatic neuroendocrine tumors (somatostatinoma).
  • Induction via dopamine β-hydroxylase promoter resulted in neuroblastoma development.
  • Murine neuroblastoma models recapitulated human disease features and responded to immunotherapy and DFMO targeting ODC1.

Conclusions:

  • c-MYC overexpression can lead to distinct but related tumor types (neuroblastoma, somatostatinoma) depending on the targeted cell.
  • Developed GEMMs are valuable tools for studying neuroblastoma and somatostatinoma origins.
  • These models provide a platform for testing novel immunotherapies and targeted treatments for neuroblastoma.

More Related Videos

Mosaic Zebrafish Transgenesis for Functional Genomic Analysis of Candidate Cooperative Genes in Tumor Pathogenesis09:45

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

Published on: March 31, 2015

11.1K
Modeling Astrocytoma Pathogenesis In Vitro and In Vivo Using Cortical Astrocytes or Neural Stem Cells from Conditional, Genetically Engineered Mice10:13

Modeling Astrocytoma Pathogenesis In Vitro and In Vivo Using Cortical Astrocytes or Neural Stem Cells from Conditional, Genetically Engineered Mice

Published on: August 12, 2014

13.4K

Related Concept Videos

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...
3.9K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.7K
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...
4.5K
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
6.4K
Cancer-Critical Genes I: Proto-oncogenes01:33

Cancer-Critical Genes I: Proto-oncogenes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
8.7K
Cancers Originate from Somatic Mutations in a Single Cell02:21

Cancers Originate from Somatic Mutations in a Single Cell

Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...
11.7K