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BRCA1 causes ovarian cancer through indirect, biochemical route

sa cells," Dubeau says. "This collaboration was essential to the project's success."

What Dubeau and his colleagues found was that while mutating the BRCA1 gene in granulosa cells did indeed give rise to ovarian tumors, those tumors did not arise in granulosa cells. Instead, when the tumor cells were analyzed, they were found to be epithelial cells very similar to those found in human ovarian cancers, with perfectly intact, functioning copies of the BRCA1 gene.

"What this says is that the cells that control the menstrual cycle, the ovarian granulosa cells, also control ovarian tumor development, but from a distance," Dubeau explains. The most likely scenario, he says, is that the granulosa cells normally give off a chemical signal that stops the epithelial cells from growing out of control. When that chemical signal disappears or is muted by a mutation in the BRCA1 gene, the epithelial cells don't get the message, and keep on growing and dividing. The result: ovarian cancer.

This finding is actually good news for scientists and physicians trying to figure out new ways to treat ovarian cancer. If the cancer had arisen in the same cells that had the BRCA1 mutation, the only way to interfere would be to correct the mutation. In this case, however, there's a mediator-a biochemical of some sort-that scientists might be able to replace in people with identified BRCA1 mutations, making their risk of ovarian cancer drop precipitously.

In addition, once the chemical messenger that's affected has been identified, it will be much easier to diagnose a predisposition to ovarian cancer or pinpoint just who is at risk, simply by measuring the chemical's levels.

"The consequence of this finding," Dubeau says, "is that ovarian cancer is the result of some biochemical problem that may be correctable or preventable. That's what makes this finding so exciting."

Dubeau points out that women with BRCA1 mutations are also predisposed to canc
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Source:University of Southern California


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