Breast Cancer Gene Affects Brain Development
Kirill Stasevich, Compulenta
Mutations in the BRCA1 gene are considered to be so strongly associated with malignant tumors of the mammary glands and ovaries that more than half of the women in whom they are found undergo preventive mastectomy: to prevent cancer from starting, their mammary glands are removed in advance. BRCA1 encodes a protein that monitors the state of DNA, so mutations in this gene lead to damage to the genome, which opens the way for cancer.
But this is what concerns the mammary glands and ovaries, but what this gene does in other organs and tissues, scientists did not know for a long time. However, it was known that mice without BRCA1 die shortly after birth, but this only spoke about the general versatility of the gene, nothing more.
A few years ago, researchers from the Inder M. Verma laboratory at the Salk Institute (USA) noticed that the BRCA1 gene is especially active in the neuroectoderm – the layer of the embryo body from which nerve stem cells are then obtained, and then mature nerve cells. It seems that BRCA1 had something to do with the development of the nervous system, and to test this, the researchers selectively turned it off in neural stem cells.
The assumption was more than justified: in animals with BRCA1 turned off, the brain developed only by a third of its normal size, and the areas responsible for learning and memory were especially greatly reduced. In addition, such animals showed ataxia, that is, the inability to adequately control the muscles and maintain balance.
According to the authors of the work in PNAS (Pao et al., Role of BRCA1 in brain development), stem cells without BRCA1 divided as usual, but too large a proportion of new cells died. BRCA1 protects cellular DNA from damage during repackaging, which occurs during division. But if it is not there, then the damage accumulates, and the ATM kinase enzyme comes into play, which senses breaks in DNA and triggers the mechanism of cell death. Some cells still survive, but because of the troubles with DNA, they turn out to be deformed and do not add up to an organized system. And this again cannot but affect the work of the brain.
In fact, BRCA1 does the same job as in ovarian and mammary cells: it protects DNA from damage. However, the "breakdown of protection" due to mutations leads to other consequences: instead of a tumor, the cells simply die (although, according to the researchers, the disorganization of the surviving nerve cells can be compared with the disorganization of a tumor). But why, then, do women with mutations in this gene have brains that seem to be in perfect order? Probably due to the fact that humans have some proportion of normal, unmutated BRCA1 genes, whereas in mice in the experiment, mutations were introduced into all cells preceding the nervous system.
It is known that in microcephaly, when the brain fails to grow larger than the brain of a chimpanzee, genes that directly control the level of BRCA1 do not work well in humans. Therefore, it is quite possible that the development of the human brain was associated with this gene, which is now being discussed most often in the context of "female" tumors. Here we can recall another study concerning the evolutionary relationship between the big brain and cancer, but in that work it was said about the direct interdependence of both, that the increased probability of a malignant tumor was the price for brain development. In the case of BRCA1, oncological health and a normal large brain are, let's say, on the same side of the barricades: for both, the absence of mutations in this gene is necessary.
Prepared based on the materials of ScienceNOW: Famous Breast Cancer Gene Could Affect Brain Growth.
Portal "Eternal youth" http://vechnayamolodost.ru20.03.2014