by Sean Henahan, Access Excellence

NASHVILLE- The BRCA1 gene, previously implicated in the development of rare familial forms of breast cancer, also appears to play a role in much more common types of non-inherited breast cancers, report researchers from Vanderbilt University Medical Center

The discovery last year of the location of the BRCA1 gene was the culmination of a furious competition by more than a dozen laboratories around the world. However, mutations in this gene were reported to be associated with only some five percent of breast cancers.

The new study indicates that BRCA1 is involved in the development of sporadic breast cancers in a way that does not involve mutations of the gene. The researchers found BRCA1's normal function is to slow cell growth, and that less BRCA1 is expressed in non-familial types. This could be a vital clue, since cancer is a process of unchecked cell growth.

"BRCA1 is not just associated with hereditary breast cancer. This is important because the inherited form of breast cancer accounts for fewer than 5 percent of all breast cancer cases. In cancer genetics, you can find hereditary cancer genes. Then you hope that the same genes are involved in the more common sporadic cancer, said Dr. Jeffrey T. Holt, associate professor of Cell Biology and Pathology, Vanderbilt University. Dr. Holt and colleagues had previously developed a new method for isolating breast cells (normal, precancerous and cancerous) from connective and other tissue. This led to the development of permanent genetic libraries which were used in the present study. The researchers found that expression of the BRCA1 gene was decreased up to tenfold in invasive breast cancers compared to normal tissue. To test the hypothesis that expression of BRCA1 inhibits cell growth, the researchers manipulated both normal and cancerous breast cells so there would be no BRCA1 being expressed. Stopping BRCA1 in breast cells made them grow faster, Holt said.

BRCA1 proved to be very stable in the normal cell samples. They level of the gene expression was found to be increased in precancerous cells. This supports the hypothesis that the breast cells' movement toward cancer triggers BRCA1 to become more active as a way to inhibit cell growth. BRCA1 levels then decrease as the cells become cancerous, allowing cell growth to progress unchecked. Why this happens is unknown at present

"This paper provides the first hard evidence as to what the function of BRCA1 may be, and it makes sense with our finding that it is decreased in invasive lesions," said Dr. Roy A. Jensen, assistant professor of Pathology and Cell Biology at Vanderbilt.

BRCA1 is proving to be a very complicated gene, with a great many mutations, and developing a screening test for it will be very challenging, Holt said. However, the latest evidence from this and other studies suggests that the BRCA1 gene may play a role in the future diagnosis and treatment of not only inherited breast and ovarian cancer but also the much more common sporadic forms, Holt said.

The current research appears in the April issue of the journal Nature Genetics.

BRCA1 also appears to be involved in the development of ovarian cancer. Another study reported in the same issue of Nature Genetics concluded that BRCA1 was flawed in at least 10 percent of sporadic cases of ovarian cancer.

Breast cancer is the most common cancer among women and the second leading cause of death from cancer in women (after lung cancer). The average woman in the U.S. has a one in nine chance of developing breast cancer by the age of 85. Ovarian cancer accounts for five percent of cancers among women.

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