Featured Research

from universities, journals, and other organizations

Research Using Mouse Models Reveals A Novel Key Player In The Initiation Of Colon Cancer

Date:
February 10, 2005
Source:
Cold Spring Harbor Laboratory
Summary:
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.

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.


Story Source:

The above story is based on materials provided by Cold Spring Harbor Laboratory. Note: Materials may be edited for content and length.


Cite This Page:

Cold Spring Harbor Laboratory. "Research Using Mouse Models Reveals A Novel Key Player In The Initiation Of Colon Cancer." ScienceDaily. ScienceDaily, 10 February 2005. <www.sciencedaily.com/releases/2005/02/050205073530.htm>.
Cold Spring Harbor Laboratory. (2005, February 10). Research Using Mouse Models Reveals A Novel Key Player In The Initiation Of Colon Cancer. ScienceDaily. Retrieved September 17, 2014 from www.sciencedaily.com/releases/2005/02/050205073530.htm
Cold Spring Harbor Laboratory. "Research Using Mouse Models Reveals A Novel Key Player In The Initiation Of Colon Cancer." ScienceDaily. www.sciencedaily.com/releases/2005/02/050205073530.htm (accessed September 17, 2014).

Share This



More Health & Medicine News

Wednesday, September 17, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

President To Send 3,000 Military Personnel To Fight Ebola

President To Send 3,000 Military Personnel To Fight Ebola

Newsy (Sep. 16, 2014) President Obama is expected to send 3,000 troops to West Africa as part of the effort to contain Ebola's spread. Video provided by Newsy
Powered by NewsLook.com
Obama Orders Military Response to Ebola

Obama Orders Military Response to Ebola

AP (Sep. 16, 2014) Calling the Ebola outbreak in West Africa a potential threat to global security, President Barack Obama is ordering 3,000 U.S. military personnel to the stricken region amid worries that the outbreak is spiraling out of control. (Sept. 16) Video provided by AP
Powered by NewsLook.com
UN: 20,000 Could Be Infected With Ebola by Year End

UN: 20,000 Could Be Infected With Ebola by Year End

AFP (Sep. 16, 2014) Nearly $1.0 billion dollars is needed to fight the Ebola outbreak raging in west Africa, the United Nations say, warning that 20,000 could be infected by year end. Duration: 00:40 Video provided by AFP
Powered by NewsLook.com
Obama: Ebola Outbreak Threat to Global Security

Obama: Ebola Outbreak Threat to Global Security

AP (Sep. 16, 2014) President Obama is ordering U.S. military personnel to West Africa to deal with the Ebola outbreak, which is he calls a potential threat to global security. (Sept. 16) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

    Technology News



    Save/Print:
    Share:

    Free Subscriptions


    Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

    Get Social & Mobile


    Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

    Have Feedback?


    Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
    Mobile: iPhone Android Web
    Follow: Facebook Twitter Google+
    Subscribe: RSS Feeds Email Newsletters
    Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins