Related Experiment Video

Updated: Jul 11, 2026

HOX Loci Focused CRISPR/sgRNA Library Screening Identifying Critical CTCF Boundaries
10:10

HOX Loci Focused CRISPR/sgRNA Library Screening Identifying Critical CTCF Boundaries

Published on: March 31, 2019

Homeobox protein CDX2 reduces Cox-2 transcription by inactivating the DNA-binding capacity of nuclear factor-kappaB

Hiroyuki Mutoh1, Hiroko Hayakawa, Hirotsugu Sakamoto

  • 1Department of Medicine, Division of Gastroenterology, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, 329-0431, Japan.

Journal of Gastroenterology
|September 19, 2007
PubMed
Abstract

Insights

The tumor suppressor Cdx2 (CDX2) inhibits cyclooxygenase-2 (COX-2) by blocking the transcription factor NF-kappaB's DNA binding. This finding reveals a mechanism linking CDX2 loss to COX-2 overexpression in colorectal cancer.

Area of Science:

  • Molecular biology
  • Cancer research
  • Gastroenterology

Background:

  • Cyclooxygenase-2 (COX-2) is overexpressed in human colon cancer.
  • Cdx2 (CDX2) is a tumor suppressor gene involved in colon cell differentiation.
  • The link between CDX2 downregulation and COX-2 overexpression in colorectal cancer is unclear.

Purpose of the Study:

  • Investigate the mechanistic link between CDX2 downregulation and COX-2 upregulation in colorectal carcinoma.
  • Elucidate how CDX2 influences COX-2 expression at the molecular level.

Main Methods:

  • Examined gene expression using immunoblotting, RT-PCR, and promoter analysis.
  • Quantified promoter transactivation with a luciferase construct.
  • Assessed nuclear factor-kappaB (NF-kappaB) DNA binding via electrophoretic mobility shift assays.

Main Results:

  • CDX2 significantly decreased COX-2 mRNA and protein expression transcriptionally in Caco-2 cells.
  • CDX2 interacted with the p50/p65 NF-kappaB complex in the nucleus.
  • CDX2 impeded the formation of the NF-kappaB-DNA complex essential for COX-2 transcription.

Conclusions:

  • CDX2 inhibits COX-2 transcription by interfering with NF-kappaB binding to its DNA site.
  • This mechanism provides insight into colorectal tumorigenesis.
  • Targeting this pathway could offer therapeutic strategies for colorectal cancer.

More Related Videos

3D Culturing of Organoids from the Intestinal Villi Epithelium Undergoing Dedifferentiation06:40

3D Culturing of Organoids from the Intestinal Villi Epithelium Undergoing Dedifferentiation

Published on: April 1, 2021

An Optimized Protocol for Electrophoretic Mobility Shift Assay Using Infrared Fluorescent Dye-labeled Oligonucleotides09:58

An Optimized Protocol for Electrophoretic Mobility Shift Assay Using Infrared Fluorescent Dye-labeled Oligonucleotides

Published on: November 29, 2016

Related Concept Videos

Co-activators and Co-repressors02:04

Co-activators and Co-repressors

Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
Co-activators and Co-repressors02:04

Co-activators and Co-repressors

Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
Master Transcription Regulators02:23

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
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...
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...
Eukaryotic Transcription Inhibitors01:52

Eukaryotic Transcription Inhibitors

Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a DNA...