Colon Cancer Oncogene Discovered

SUNDAY, Sept. 14 (HealthDay News) -- Researchers have identified a new genetic player in the development of colon cancer.

The findings implicate CDK8, a protein that regulates gene expression in the proliferation of colorectal cancer, the researchers found.

Should the results be validated, they could lead to new therapeutic approaches for colon cancer, as well as new screening and chemopreventative strategies, said Dr. Durado Brooks, director of prostate and colorectal cancer at the American Cancer Society.

"I think it is important work," Brooks said. "They have identified what apparently is an oncogene associated with some colorectal cancers."

Dr. William Hahn, of the Dana-Farber Cancer Institute in Boston, and his colleagues screened human colon cancer cells for genes that met three criteria: They were required for cellular proliferation, critical to regulating the WNT/beta-catenin signaling pathway known to be involved in the bulk of colon cancer cases, and also genetically amplified in cancerous cells.

"When we did that, we found one gene that fulfilled all three criteria, and that is CDK8," Hahn said.

The results were published in the Sept. 14 issue ofNature.

CDK8 is a member of the so-called mediator complex, which bridges distant protein complexes to activate expression of certain genes.

According to Hahn, the study has two take-home messages.

The first, he said, is the apparent prevalence of colorectal tumors with elevated CDK8. Of the 50 tumors that Hahn and his team analyzed, 31 (62 percent) displayed evidence of CDK8 gene amplification -- that is, the tumors contained more than the normal two copies of the gene, which usually leads to higher levels of protein expression.

"This is surprising in the sense that it occurs in a large percentage of colon cancers, and we didn't know about it," he said.

The second message involves the potential pharmacologic benefits of these results. CDK8 is a type of protein known as a kinase. Kinases are enzymes that catalyze the transfer of phosphate groups from one molecule to another. That action is like flipping a molecular switch, causing the recipient protein to turn on or off. It turns out that kinases tend to play key roles in the biochemical pathways that often go haywire in cancer, so they are popular targets for drug developers.