home   genetic news   bioinformatics   biotechnology   literature   journals   ethics   positions   events   sitemap
 
  HUM-MOLGEN -> Genetic News | search  
 

Researchers discover new gene in colon cancer

 
  December, 20 2004 12:17
your information resource in human molecular genetics
 
     
Cancer researchers at the Case Western Reserve University (Case) School of Medicine, University Hospitals of Cleveland (UHC) and the Howard Hughes Medical Institute have found a "Celebrex-like" gene that suppresses the growth of colon cancer. The researchers discovered that the gene, called 15-PGDH, is found in normal cells and is virtually undetectable in colon cancer cells. When the researchers restored the gene in tumor cells and injected them into immune-deficient mice, the mice showed little or no tumor development. The study appears in the Dec. 14 issue of the Proceedings of the National Academy of Sciences.

The gene 15-PGDH acts as an antagonist to control an enzyme called COX-2. An increase in COX-2 is a major early event in the genesis of human colon tumors.

Sanford Markowitz, M.D., the Francis Wragg Ingalls Professor of Cancer Genetics at Case and UHC and senior author of the paper, said, "This gene may represent the first of a one-two punch in colon cancer. In colon cancers a dramatic increase of COX-2 is seen. 15-PGDH would act to antagonize and check this increased COX-2 activity. Without 15-PGDH present,unchecked COX-2 goes on to cause abnormal changes on the cellular level, which may lead to tumor development."

Previous studies have shown that patients who take nonsteroidal anti-inflammatory drugs (NSAIDs), which are COX-2 inhibitors, have a lower incidence of colon cancer. COX-2 inhibitors have been shown to shrink the size of tumors in mice. Markowitz likens the 15-PGDH gene to a naturally occurring COX-2 inhibitor. (Celebrex, a popular arthritis drug, is also a COX-2 inhibitor.)

Markowitz found that 15-PGDH is directly controlled and activated by another gene, called TGF-beta. Normally, TGF-beta sends a signal that allows the colon to shed cells weekly as a way of helping to block development of colon cancers. In 1995, Markowitz discovered colon cancers have mutations that inactivate the TGF-beta pathway.

"If there is no TGF-beta signal, there is no 15-PGDH. That means the opponent to COX-2 is gone, and the COX-2 oncogene activity is unopposed," said Markowitz. "This interaction between TGF-beta and 15-PGDH points to the importance of the TGF-beta system in suppressing colon cancer. These genes give us targets that we can aim for in the development of new drugs or gene therapies that may help us treat or prevent colon cancer," said Markowitz, who is also an investigator with the Howard Hughes Medical Institute.

Lead authors on the paper are Min Yan of the departments of medicine, molecular and microbiology at Case Western Reserve University School of Medicine and the Ireland Cancer Center at University Hospitals of Cleveland, and Ronald M. Rerko of Howard Hughes Medical Institute. Also involved were researchers from the University of Kentucky and the Protein Design Laboratories in Freemont, Calif.

© 2004 Case Western Reserve University

Yan M, Rerko RM, Platzer P, Dawson D, Willis J, Tong M, Lawrence E, Lutterbaugh J, Lu S, Willson JK, Luo G, Hensold J, Tai HH, Wilson K, Markowitz SD.
From the Cover: 15-Hydroxyprostaglandin dehydrogenase, a COX-2 oncogene antagonist, is a TGF-{beta}-induced suppressor of human gastrointestinal cancers.
Proc Natl Acad Sci U S A. 2004 Dec 14;101(50):17468-17473. Epub 2004 Dec 1.


Message posted by: Frank S. Zollmann

print this article mail this article
Bookmark and Share this page (what is this?)

Social bookmarking allows users to save and categorise a personal collection of bookmarks and share them with others. This is different to using your own browser bookmarks which are available using the menus within your web browser.

Use the links below to share this article on the social bookmarking site of your choice.

Read more about social bookmarking at Wikipedia - Social Bookmarking

Latest News
Variants Associated with Pediatric Allergic Disorder

Mutations in PHF6 Found in T-Cell Leukemia

Genetic Risk Variant for Urinary Bladder Cancer

Antibody Has Therapeutic Effect on Mice with ALS

Regulating P53 Activity in Cancer Cells

Anti-RNA Therapy Counters Breast Cancer Spread

Mitochondrial DNA Diversity

The Power of RNA Sequencing

‘Pro-Ageing' Therapy for Cancer?

Niche Genetics Influence Leukaemia

Molecular Biology: Clinical Promise for RNA Interference

Chemoprevention Cocktail for Colon Cancer

more news ...

Generated by News Editor 2.0 by Kai Garlipp
WWW: Kai Garlipp, Frank S. Zollmann.
7.0 © 1995-2016 HUM-MOLGEN. All rights reserved. Liability, Copyright and Imprint.