Gene linked to 30 pct of breast cancers: study

WASHINGTON Thu Jun 14, 2007 1:23pm EDT

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WASHINGTON (Reuters) - Extra copies of a certain gene found in about a third of breast cancers may be responsible for their unchecked growth and survival, researchers reported on Thursday.

They found as many as 10 copies of the gene, called IKBKE, in some cancers. Normal cells have only two copies of IKBKE.

Multiple copies were "found in anywhere from 30 to 40 percent of breast cancers, a pretty large percentage," said Dr. William Hahn of the Dana Farber Cancer Institute and Harvard Medical School in Boston, who led the research.

"If we can think of ways to target it, (IKBKE) can become potentially very useful in the future," he said.

The gene codes for a certain kind of a protein, a kinase known as IKK-epsilon. It acts as a control switch to help regulate cell growth.

When it has too many copies, a cell can make too much of the kinase, over stimulating a series of growth signals and allowing the cell to resist death and proliferate inappropriately, the researchers reported in the journal Cell.

This signal pathway, found in all cells, goes awry in a number of cancer types.

Even some early stage breast growths the researchers examined had multiple copies of IKBKE, so cells likely gain duplicates at the start of their transformation into cancer, Hahn said.

People with these breast cancers do not inherit multiple copies from their parents. Rather, the copies seem to appear spontaneously in individual cells by mechanisms that Hahn and others do not quite understand.

Hahn's team found that cells with extra copies of the gene became addicted to making greater amounts of the protein. When the scientists prevented laboratory-grown cancer cells from making IKK-epsilon, the cells stopped growing or even died.

They are now trying to find a drug, perhaps a pill, to do the same in patients whose tumors have extra copies, Hahn said.

Gleevec, a pill made by Novartis, fights chronic myelogenous leukemia by preventing another kinase from doing its job in rapidly dividing white blood cells.

"There's a lot of similarity in how to target these things," Hahn said.

In the past, scientists either searched for potentially cancer-causing genetic mistakes in lab-grown cells, altered a cell's DNA to see what would happen to the cell or searched for genes with multiple copies in patients' tumors.

But none of these approaches alone told the whole story.

By combining all three strategies, as Hahn's team did in its study, researchers can now sift through the mess of DNA changes that typically arise in tumor cells to isolate other cancer culprits.

Breast cancer kills 500,000 people a year globally, according to the World Health Organization, and 1.2 million men and women are diagnosed with it every year

Some cases run in families and close to a dozen genes have been identified that raise this risk.

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