Signal Disruption Causes Some Ovarian Cancers

A recent study has revealed that ovarian cancer in women bearing a mutated form of the BRCA1 gene is caused by disruption of biochemical signaling that also disrupts granulosa cell regulation of epithelial cell growth.

BRCA1, known as the breast cancer gene, not only gives carriers of its mutated form an 80% chance of developing breast cancer, it also confers a 40% percent risk of developing ovarian cancer by the age of 70.

Investigators at the University of Southern California (USA) developed a line of mice lacking the BRCA1gene only in their ovarian granulosa cells. These mice were found to be prone to development of ovarian tumors. However, the tumors did not arise in granulosa tissue. Rather, the tumors originated in epithelial tissue, and they carried normal BRCA1 genes. These findings were published in the March 29, 2005, issue of Current Biology.

"Before, we thought this gene was a classical tumor suppressor,” said senior author Dr. Louis Dubeau, professor of pathology at the University of Southern California. "If that were the case, it would mean that mutation of the gene would allow the cell it is in to grow out of control and create a tumor. Instead, what we have shown is that the gene actually acts indirectly, that it disrupts interactions between different cell types. The consequence of this finding is that ovarian cancer is the result of some biochemical problem that may be correctable or preventable. That is what makes this finding so exciting.”



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