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Scientists identify a gene that may suppress colorectal cancer

PHILADELPHIA (Thurs., Mar. 22, 2007) -- In todays online edition of Genome Research, a husband-and-wife research team from Thomas Jefferson University report the discovery of a gene that, when mutated, may suppress colorectal cancer. To conduct the study, the researchers used a strain of mice that develop polyps, or small growths of tissue, in the digestive tractthe harbingers of cancer. When these mice possessed one copy of the mutated gene, the incidence of small intestinal and colon polyps were reduced by about 90%.

This gene may give us a novel target to aid in the diagnosis, prevention, and/or treatment of cancer, says Dr. Arthur Buchberg, one of the co-senior authors on the report.

The gene is called Atp5a1, and encodes an essential component of the cells energy-production machinery. Mice with two copies of mutated Atp5a1 die early in embryonic developmentprobably due to insufficient energy. The identification of a gene critical for energy production in the cell opens up an array of potential new targets for therapy.

The research team identified a duplication of DNAonly four bases in lengthin a critical part of the Atp5a1 gene. This mutation, which results in decreased levels of Atp5a1 gene expression, is the first mutation identified in the mouse Atp5a1 gene. In trypanosomes (tiny parasitic protozoa that cause African sleeping sickness), the loss of Atp5a1 gene function leads to death. To date, no mutations in the human ATP5A1 gene have been identifiedfurther supporting its essential role in the cell.

In humans, ATP5A1 is located on chromosome 18, in a region that often exhibits genetic alterations in colon tumors, says Dr. Linda Siracusa, the other co-senior investigator on the project. A better understanding of the biological function of ATP5A1 will provide insights concerning its potential role in human cancer.

Colorectal
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Contact: Maria A. Smit
smit@cshl.edu
516-422-4127
Cold Spring Harbor Laboratory
21-Mar-2007


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