Scientists identify a gene that may suppress colorectal cancer

22-Mar-2007

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 tract-the 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%.

The gene is called Atp5a1, and encodes an essential component of the cell's energy-production machinery. Mice with two copies of mutated Atp5a1 die early in embryonic development-probably 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 DNA-only four bases in length-in 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 identified-further 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."

The scientists used a strain of mice called Min (multiple intestinal neoplasia). Min mice carry mutations in the Apc gene, which causes the development of intestinal tumors. Inactivation of the corresponding gene (APC) in humans is considered a key event in the development of colorectal cancer.

Tumor development is regulated by modifier genes, which may function to enhance or suppress tumor initiation, growth and/or progression. Atp5a1 is a modifier gene, and it is located on the same chromosome as Apc in mice. Interestingly, the results suggest that the mutant Atp5a1 gene caused the death of tumor cells, primarily when it was present on the same chromosome as the mutant Apc gene.

Original publication: Baran, A.A., Silverman, K.A., Zeskand, J., Koratkar, R., Palmer, A., McCullen, K., Curran, W.J., Bocker Edmonston, T., Siracusa, L.D., Buchberg, A.M; "The Modifier of Min 2 (Mom2) locus: embryonic lethality of a mutation in the Atp5a1 gene suggests a novel mechanism of polyp suppression."; Genome Res.2007.

https://www.bionity.com/en/news/62904/scientists-identify-a-gene-that-may-suppress-colorectal-cancer.html