Scientists find link between brain development and breast cancer gene
It is well known that females with a BRCA1 gene mutation are at a much higher risk of developing breast and ovarian cancers. Now, researchers from the Salk Institute in La Jolla, CA, have discovered what they describe as a "crucial" link between brain development and the BRCA1 gene.
The research team, including Inder Verma of the Laboratory of Genetics at Salk, recently published their findings in the journal Proceedings of the National Academy of Sciences.
According to the investigators, some women who are genetically susceptible to breast cancer, such as those with BRCA1 mutations, experience brain seizures. In their study, the team found that the BRCA1 gene played an important part in healthy brain development in mice - a finding that may help explain the occurrence of such brain seizures.
The investigators say not only could these findings lead to a better understanding of neurological damage in some individuals who are at higher risk of breast cancer, but they could also provide a better understanding of brain evolution.
Elimination of BRCA1 gene led to brain underdevelopment
To reach their findings, the research team first deleted the BRCA1 gene in neural stem cells. This led to the underdevelopment of certain brain regions.
The top row shows normal brain development, while the bottom row shows brain development as a result of BRCA1 gene deletion.
Image credit: Salk Institute for Biological Studies
They found that the cortex of the brain only developed two layers, rather than the usual six layers. The cerebellum of the brain is usually made up of several folds, but in this case, it was almost completely smooth. The brain region that processes odor information - the olfactory bulb - was poorly developed and severely disordered.
In addition, the researchers found that neurons died shortly after developing and the ones that did remain were abnormal.
When deleting the BRCA1 gene in mouse models, the team found that this abnormal brain development interfered with balance, motor skills and other core functions.
BRCA1 gene 'plays crucial part in organization of neurons'
Explaining why eliminating the BRCA1 gene had this effect, the researchers refer to a previous study, in which they found that DNA is not "packaged" correctly when protein coded by the BRCA1 gene is missing. This means DNA is more fragile and more likely to break when it attempts to replicate.
The team says this new study builds on this information; they found that without the protective proteins of the BRCA1 gene, DNA strands remain broken. This causes a molecule called ATM kinase to trigger a cellular "suicide" pathway that involves a protein called p53. According to the researchers, this pathway is important in cancer research, as it helps block replication of damaged cells.
The research team explains their findings in the video below:
When both the BRCA1 gene and p53 protein were deleted, this caused brain neurons to grow at a normal rate. However, the team found that the neurons were still disorganized and cells were facing the wrong direction.
From this, the researchers hypothesize that the BRCA1 gene plays a part in the positioning of neurons. They believe the gene acts as an anchor for the centromere of DNA - the chromosome arms needed for cell replication. It informs the new cell of which way to grow and guides the organization of brain layers to ensure normal development.
Commenting on the findings, Verma says:
"Previously, people associated mutations or deletions of BRCA1 with breast and ovarian cancer. Our paper goes beyond this link to explain the protective mechanism of BRCA1 in the brain.
It is remarkable that BRCA1 has such a significant effect on the brain, especially size. This work leads us to a better understanding of how to protect neurons."
Since the BRCA1 gene appears to regulate the centromere of DNA, the researchers say that studying the gene further will lead to a greater understanding of the evolution of mammalian brains.
Furthermore, the team says the findings explain why some breast cancer patients have brain seizures. They add that this could lead to the identification and treatment of individuals at higher risk of breast cancer who may be predisposed to seizures.
Earlier this year, Medical News Today recently reported on a study suggesting that young women with BRCA1 mutations should have their ovaries removed earlier to further reduce their risk of ovarian cancer.
Written by Honor Whiteman
Copyright: Medical News Today
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