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

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 dev eloped 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.


'"/>

Source:ScienceDaily


Related biology news :

1. Researchers discover way to make cells in the eye sensitive to light
2. Quantum Dots Research Leads to New Knowledge about Protein Binding in Plants
3. Researchers find how protein allows insects to detect and respond to pheromones
4. Researchers Uncover Key Step In Manufacture of Memory Protein
5. Research advances quest for HIV-1 vaccine
6. Research on Worms Yields Clues on Aging
7. Researchers reveal the infectious impact of salmon farms on wild salmon
8. Researchers identify target for cancer drugs
9. Weill Cornell Research Reveals Secrets Of Trafficking Within Cells
10. Researchers discover molecule that causes secondary stroke
11. Researchers find missing genes of ancient organism
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:2/9/2016)... -- Vigilant Solutions announces today that an agency used its ... lead in a difficult homicide case. The agency then used ... suspect vehicle. Due to the ongoing investigation, the agency name ... the agency,s request. --> --> ... found deceased at an intersection here in the City. He ...
(Date:2/3/2016)... --> --> ... Fingerprint Identification System Market by Component (Hardware and Software), ... Finance, Government, Healthcare, and Transportation) and Geography - Global ... expected to be worth USD 8.49 Billion by 2020 ... 2020. The transformation and technology evolution from the manual ...
(Date:2/2/2016)... 2016 Checkpoint Inhibitors for Cancer – ... Are you interested in the future of cancer ... inhibitors. Visiongain,s report gives those predictions to 2026 ... level. Avoid falling behind in data or ... revenues those emerging cancer therapies can achieve. There ...
Breaking Biology News(10 mins):
(Date:2/9/2016)... ... February 09, 2016 , ... Clinovo , the ... validated Electronic Data Capture (EDC) system ClinCaptureand its new Contract Research Organization (CRO) ... 2016 Conference in San Mateo, California on February 10th and 11th. Watch ...
(Date:2/9/2016)... Lawrenceville, NJ (PRWEB) , ... February 09, 2016 ... ... Diane Dorman, former Vice President for Public Policy for the National Organization for ... and patient advocacy groups to ensure their voices are heard throughout the drug ...
(Date:2/9/2016)... February 9, 2016 Three-Year Initiative Supports ... to Take Part in Life-Changing Camp ... designed to positively affect the lives of children born with rare ... --> SHPG ) is announcing a new initiative designed to ... well as the future of rare disease care. --> ...
(Date:2/8/2016)... PLYMOUTH MEETING, Pa. , Feb. 8, 2016 /PRNewswire-USNewswire/ ... place of standard bone cement products to prevent infection ... a question that the experts at ECRI Institute have ... Cement: Fighting Infection or Fighting Your Bottom Line?" ... or Fighting Your Bottom Line?" --> ...
Breaking Biology Technology: