Related Experiment Video
Updated: Apr 15, 2026
Real-time Imaging of Myeloid Cells Dynamics in ApcMin/+ Intestinal Tumors by Spinning Disk Confocal Microscopy
Published on: October 6, 2014
Inactivation of Itf2 promotes intestinal tumorigenesis in Apc(Min/+) mice
Jessica I Grill1, Andreas Herbst2, Lydia Brandl3
1Department of Medicine II, University of Munich, 81377 Munich, Germany; Institute of Molecular Animal Breeding and Biotechnology, Gene Center, University of Munich, 81377 Munich, Germany.
Abstract:
Deregulation of Wnt/β-catenin signaling following inactivation of the adenomatous polyposis coli (APC) tumor suppressor gene is frequently found in colorectal cancer. We have previously shown that levels of ITF-2B, encoded by the β-catenin target gene ITF2 that is located on the tumor suppressor gene locus 18q21, are increased in colonic adenomas with deregulated β-catenin activity. However, during tumor progression ITF-2B levels are reduced, suggesting that ITF-2B interferes with tumor development. To investigate the role of ITF2 in intestinal tumorigenesis, we specifically inactivated Itf2 in the intestinal epithelium of Apc(Min/+) mice. We found that genetic disruption of Itf2 on the Apc(Min/+) background results in earlier death and a significant increase in tumor number and size in the small intestine. Based on these data Itf2 acts as a tumor suppressor gene of the intestinal tract that inhibits tumor initiation and growth.
Insights
The ITF2 gene acts as a tumor suppressor, inhibiting the initiation and growth of intestinal tumors. Its inactivation in mice led to increased tumor development and reduced survival, highlighting its critical role in preventing colorectal cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Wnt/β-catenin signaling pathway deregulation is common in colorectal cancer, often due to adenomatous polyposis coli (APC) gene inactivation.
- Increased ITF-2B levels were observed in early colonic adenomas with Wnt/β-catenin activity, but decreased during tumor progression.
- This suggests a potential tumor-suppressive role for ITF-2B and its encoding gene, ITF2.
Purpose of the Study:
- To investigate the role of the ITF2 gene in intestinal tumorigenesis.
- To determine if ITF2 functions as a tumor suppressor in the context of APC inactivation.
Main Methods:
- Specific inactivation of the Itf2 gene in the intestinal epithelium of Apc(Min/+) mice.
- Analysis of tumor development, size, and survival rates in genetically modified mice.
Main Results:
- Genetic disruption of Itf2 in Apc(Min/+) mice led to earlier mortality.
- A significant increase in both the number and size of intestinal tumors was observed.
- These findings indicate that Itf2 normally suppresses tumor initiation and growth.
Conclusions:
- ITF2 functions as a tumor suppressor gene in the intestinal tract.
- Loss of ITF2 function promotes intestinal tumor development and progression.
- Targeting ITF2 could be a potential strategy in colorectal cancer therapy.
Related Concept Videos
01:12Role Of Notch Signalling In Intestinal Stem Cell Renewal
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
02:23Abnormal Proliferation
01:12Loss of Tumor Suppressor Gene Functions
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...
01:31The Intrinsic Apoptotic Pathway