Molecular pathway provides clues about BRCA1 role in breast cancer

Washington, Jan 16 : US researchers have discovered a breast cancer gene's new role in repairing damaged DNA, which might help explain why women who inherit a mutated copy of the gene are at a high risk for developing breast cancer.

The study, led by Craig Bennett, Ph.D., a researcher in Duke's Department of Surgery, stated that the finding could lead to more effective therapies for women with and without mutated copies of the BRCA1 (Breast Cancer 1, early onset) gene.

"Since it was discovered in 1994, BRCA1 and its role in preventing and causing cancer has been intensely studied, and our research represents an important piece of the puzzle," Bennett said.

"This study has identified an important mechanism by which BRCA1 comes into play when DNA -- the basis for all cell function -- is damaged. We have shown that this theory holds up not just in scientific models but in human breast cancer cells as well," he added.

In the study, the researchers looked at yeast to demonstrate that a molecular pathway that is particularly susceptible to BRCA1 influence is also crucial to normal cell function.

"The BRCA1 pathway we discovered is directly involved with the critical process of transcription, in which RNA acts as a messenger between DNA and the making of proteins," Bennett said.

Bennett said that DNA damage is a normal result of exposure to environmental agents, such as carcinogens, and the response to this damage can be influenced by other normal human processes such as aging and hormonal changes.

It's what happens to RNA (Ribonucleic acid) transcription after damage occurs in DNA that is BRCA1-dependent.

"We found that BRCA1 acts together with transcription to detect DNA damage and to signal the cell to repair itself. When BRCA1 does not function correctly, as when it is mutated, DNA damage remains un-repaired and cancer can occur," Bennett said.

The researchers applied their findings in yeast to human breast cancer cells, with the same results.

"The fact that we were able to duplicate our results in human breast cancer cells is hugely important. Yeast is a wonderful model organism that has been used to make significant discoveries in many areas of science and medicine, including Parkinson's and Alzheimer's diseases, but the ability to replicate results in human cells is key," Bennett said.

Bennett said the discovery would lay the groundwork for further investigation of the role of BRCA1 and possibly lead to new therapeutic strategies targeting the genes or protein products within this pathway.

The study is published in the journal PLoS ONE.

ANI