Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Research using mouse models reveals a novel key player in the initiation of colon cancer

04.02.2005


Gastric and colorectal cancers account for more than 1 million deaths worldwide every year and several research groups have been working to identify the molecular events that result in the initiation and progression of these tumors. It has been established that interfering with the function of one gene, called Adenomatous Polyposis Coli (APC) has a profound effect on the cells lining the innermost layer of the colon (called the epithelium) and causes them to lose control over their proliferation leading to tumors.

Now Klaus Kaestner from the University of Pennsylvania School of Medicine has headed a study that identifies another molecular player influencing the initiation of colon cancers. This study will be published in the February 1 issue of the journal Genes and Development.

An animal model with an inactivating mutation within the mouse equivalent of the APC gene displays very similar pathology as seen in human colon cancers and develop tumor growths called polyps in their colons, eventually leading to death. Inactivating the APC gene was found, as in human cells, to cause the accumulation of a protein called beta-catenin in the nuclei of these cells.



Kaestner’s group had earlier published research on a transcription factor called Foxl1 that is also expressed in the colon, but in a different layer of cells, adjacent to the epithelium, called the mesenchyme. They had seen that mice that are deficient for the Foxl1 protein show a similar accumulation of the beta-catenin protein in the epithelium layer, yet they do not get cancers. However, combining the Foxl1 deficiency with an inactive APC gene had drastic outcomes. The group compared animals that were partially deficient for APC (containing one normal copy of the APC gene and one mutant inactive copy) in the presence or absence of Foxl1. Both animals developed tumors, however, in the absence of Foxl1, tumor frequency was more than 7-fold higher.

In addition, the animals developed tumors in the stomach. None of the tumors seen in either case were invasive leading to the conclusion that the Foxl1deficiency affects early stages in tumor formation. Additional analysis revealed that the Foxl1 deficiency affected the onset of tumor formation, accelerating them to arise in 1/3rd of the normal time. The authors examined the integrity of the APC gene in these tumor cells and found that more than ninety per cent of the tumors had lost the normal copy of the APC gene and now were completely deficient.

What is the significance of these results on understanding the initiation of colon cancer? A deficiency of Foxl1 in the mesenchymal layer of the colon leads to altered signaling to the epithelium layer and results in increased cell proliferation and turnover of this layer. In people with a genetic predisposition, like those with Familial Adenomatous Polyposis, or environmental stress that generates a spontaneous mutation in the APC gene, mutations in the Foxl1 gene or its targets may dramatically increase the likelihood that the second normal copy of the APC gene is lost or mutated, leading to the initiation of tumor formation.

This study sets a new paradigm for gastrointestinal tumorigenesis, in that genetic events outside the epithelial layer itself have a profound effect on tumor initiation. Thus it appears likely that this study will foster additional research into other mesenchymal genetic modifiers, and into potential therapeutic approaches that affect the signaling between the two cell layers.

Heather Cosel | EurekAlert!
Further information:
http://www.cshl.edu

More articles from Life Sciences:

nachricht Researchers target protein that protects bacteria's DNA 'recipes'
21.08.2018 | University of Rochester

nachricht Protein interaction helps Yersinia cause disease
21.08.2018 | Schwedischer Forschungsrat - The Swedish Research Council

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: It’s All in the Mix: Jülich Researchers are Developing Fast-Charging Solid-State Batteries

There are currently great hopes for solid-state batteries. They contain no liquid parts that could leak or catch fire. For this reason, they do not require cooling and are considered to be much safer, more reliable, and longer lasting than traditional lithium-ion batteries. Jülich scientists have now introduced a new concept that allows currents up to ten times greater during charging and discharging than previously described in the literature. The improvement was achieved by a “clever” choice of materials with a focus on consistently good compatibility. All components were made from phosphate compounds, which are well matched both chemically and mechanically.

The low current is considered one of the biggest hurdles in the development of solid-state batteries. It is the reason why the batteries take a relatively long...

Im Focus: Color effects from transparent 3D-printed nanostructures

New design tool automatically creates nanostructure 3D-print templates for user-given colors
Scientists present work at prestigious SIGGRAPH conference

Most of the objects we see are colored by pigments, but using pigments has disadvantages: such colors can fade, industrial pigments are often toxic, and...

Im Focus: Unraveling the nature of 'whistlers' from space in the lab

A new study sheds light on how ultralow frequency radio waves and plasmas interact

Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...

Im Focus: New interactive machine learning tool makes car designs more aerodynamic

Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.

When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.

Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

LaserForum 2018 deals with 3D production of components

17.08.2018 | Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

 
Latest News

Air pollution leads to cardiovascular diseases

21.08.2018 | Ecology, The Environment and Conservation

Researchers target protein that protects bacteria's DNA 'recipes'

21.08.2018 | Life Sciences

A paper battery powered by bacteria

21.08.2018 | Power and Electrical Engineering

VideoLinks
Science & Research
Overview of more VideoLinks >>>