Related Experiment Video

Updated: Sep 28, 2026

Modeling Oral-Esophageal Squamous Cell Carcinoma in 3D Organoids
10:43

Modeling Oral-Esophageal Squamous Cell Carcinoma in 3D Organoids

Published on: December 23, 2022

Pharmacologic unmasking of epigenetically silenced tumor suppressor genes in esophageal squamous cell carcinoma

Keishi Yamashita1, Sunil Upadhyay, Motonobu Osada

  • 1Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University, 720 Rutland Avenue, Ross Building 818, Baltimore, MD 21205, USA.

Cancer Cell
|December 25, 2002
PubMed

Insights

Researchers identified tumor suppressor genes in esophageal squamous cell carcinoma (ESCC) by reactivating silenced genes. This approach revealed key genes like CRIP-1, Apolipoprotein D, and Neuromedin U with potent growth suppressive activity in ESCC cells.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • Esophageal squamous cell carcinoma (ESCC) is characterized by the inactivation of tumor suppressor genes.
  • Epigenetic silencing, particularly promoter methylation, is a common mechanism for gene inactivation in cancer.
  • Identifying novel tumor suppressor genes is crucial for developing targeted therapies.

Purpose of the Study:

  • To comprehensively survey inactivated tumor suppressor genes in ESCC.
  • To investigate the role of epigenetic silencing in tumor suppressor gene inactivation.
  • To identify functionally validated tumor suppressor genes in ESCC.

Main Methods:

  • Functional reactivation of epigenetically silenced genes using 5-aza-2'-deoxycytidine and trichostatin A.
  • Microarray analysis of 12599 genes to identify candidate tumor suppressor genes.
  • Analysis of CpG island methylation in promoter regions.
  • Validation of gene methylation and mRNA silencing in ESCC cell lines and primary tumors.
  • Colony focus assays to assess the growth suppressive activity of candidate genes in ESCC cells.

Main Results:

  • A comprehensive survey identified 58 candidate tumor suppressor genes.
  • 76% (44/58) of identified genes possessed dense CpG islands in their promoter regions.
  • Promoter methylation was observed in 13/22 tested genes in cell lines and 10/22 in primary ESCC, correlating with mRNA silencing.
  • Three genes (CRIP-1, Apolipoprotein D, and Neuromedin U) demonstrated potent growth suppressive activity in ESCC cells.

Conclusions:

  • Pharmacologic reversal of epigenetic silencing is an effective strategy for identifying tumor suppressor genes in human cancers.
  • CRIP-1, Apolipoprotein D, and Neuromedin U are validated tumor suppressor genes in ESCC with significant growth inhibitory functions.
  • Targeting epigenetically silenced tumor suppressor genes represents a promising therapeutic avenue for ESCC.

More Related Videos

Development of Compendium for Esophageal Squamous Cell Carcinoma03:36

Development of Compendium for Esophageal Squamous Cell Carcinoma

Published on: April 12, 2024

Related Concept Videos

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...
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
Epigenetic Regulation01:37

Epigenetic Regulation

Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
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.
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
Pharmacogenomics: Identification of New Drug Targets01:29

Pharmacogenomics: Identification of New Drug Targets

Advances in genomics have profoundly influenced drug discovery by increasing both the speed and accuracy of pharmaceutical development. Pharmacogenomics, which examines how genetic variation influences drug response, facilitates the identification of novel therapeutic targets and enables patient stratification for personalized treatment. These strategies contribute to improved drug efficacy, minimized adverse effects, and more efficient clinical trial design.Mapping genetic differences...