 Researchers are one step closer to knowing why women with BRCA2 gene mutations have an increased risk for breast and ovarian cancer. A study published in the Jan. 26 issue of the journal Cell describes a partnership between BRCA2 and a newly discovered gene called BRAF35.
Scientists believe the genes work together to regulate how cells divide. BRAF35 is located in a region of chromosome 19 previously linked to ovarian cancer.
Researchers from the Wistar Institute, the University of Pennsylvania, and Fox Chase Cancer Center in Philadelphia inactivated BRCA2 or BRAF35 function in human cells grown in laboratory dishes and found many of the cells were unable to divide at a normal pace. In the experiment, 80% of normal cells with active genes completed their division but only 40% to 50% of cells lacking BRCA2 or BRAF35 divided. "This indicated these genes influence progression of the cells through the cell cycle ? a role which had not really been anticipated for BRCA2 before," says lead researcher Ramin Shiekhattar, PhD, assistant professor at the Wistar Institute.
Unanswered Questions
Earlier studies suggested that BRCA2 is a tumor suppressor, so a mutation would make cells divide out of control. What is confusing to researchers is that, when BRCA2 or BRAF35 proteins are absent, cells appear to divide more slowly instead. However, previous studies found that BRCA2-deficient mice often do develop abnormal chromosomes that are similar to those found in some cancers.
Taken together, these results suggest that BRCA2 inactivation does more than slow down cell division. It also may interfere with the process that usually divides chromosomes and assures equality between each of the two new cells. When this delicate process is not working properly, chromosomes may break and reattach in ways that affect their growth-regulating genes, ultimately causing a cancer to form.
Shiekhattar''s approach is to study how BRCA2 normally functions in the cell. "Once we can answer that, then we can understand what may go wrong when it is mutated," he says. Dual Functions for BRCA2?
Other studies have linked BRCA2 with DNA repair. Often, cellular repair and division go hand-in-hand because the cell has checkpoints to ensure everything is working properly before it divides. Shiekhattar says BRCA2 and BRAF35 might be involved in both of these processes.
"This article provides a lot of evidence that BRCA2 does more than what we thought it did in the past, and that the whole story is much more complicated than we thought," says Donella Wilson, PhD, scientific program director for the American Cancer Society.
"Understanding how and when BRCA2 functions in the cell is important because it will allow scientists to target better drugs for breast cancers that result from mutations of the gene," she adds. "This might even lead to new strategies for preventing breast or ovarian cancer in women at high risk because of inherited BRCA2 mutations. However, such practical applications of this discovery will require years of additional research."
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