Study Shows Mechanism BRCA1 Damages Breast Cells

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Breast cancer is a malignancy emerging from the breast tissue. It is one of the malignancies commonly suffered by most women, compared with men. It caused about 450,000 deaths globally in 2008. Survival rates are generally good, with the novel discoveries derived from relevant studies. Recently, the researchers from Johns Hopkins Kimmel Cancer Center demonstrated in their study that the inactivation of gene BRCA1 leads to vulnerability of breast cells become to cancer. This susceptibility stems from their decreased ability in repairing DNA injury.

Moreover, it was noted that the primary risk factor for hereditary malignant breast neoplasm is the inherited mutation in the gene BRCA1 that necessitates close monitoring and prompt prophylactic interventions, like preventive mastectomy.  This study can aid researchers in developing a medication, which can prevent hereditary breast malignancy, and tools in identifying patients who are benefited from these preventive treatments. This was published on October 25 in the Proceedings of the National Academy of Sciences.

The gene BRCA1 is thought to be a tumor suppressor. Commonly, cancer does not result from the loss of a copy of such gene, because each person is born with 2 copies of every gene (one from every parent). Also, the second copy is enough to maintain healthy cells. Furthermore, researchers stated that cancer development only occurs when there is damage to the second copy of the gene. It was further observed in mouse models that injury to genes (i.e. TP53) happened before the second BRCA1 copy is damaged.

The team utilized new technology in inserting a single copy of a typical BRCA1 mutation into normal breast cells. Their fundamental theory involves “genomic instability”. This is the original inactivation of a single copy of BRCA1 that can lead to further DNA mutations beyond normal. Moreover, Park elaborated that because the protein coded by BRCA1 has a role in repairing DNA damages, it is logical that its inactivation can lead to reduced cell resistance to DNA mutations. He added that the effect of losing a copy of BRCA1 was difficult to study and model.

The researchers chose cell lines from non-cancerous human breast epithelial cells (where BRCA1-related cancers emerge) to test their presumption. Then, an advanced gene-targeting means was utilized in generating novel cell lines, which have typical cancer-related BRCA1 mutation in only one gene copy. Afterwards, to make a comparison of DNA repair activity, there were tests on both cell types: cells with BRCA1 mutation and original cells with 2 healthy BRCA1 copies. Furthermore, they discovered that the BRCA1-mutated cells would probably die if they had an exposure to DNA-damaging chemotherapeutic agents or radiation. Furthermore, there were genetic losses in BRCA1- mutated cells (which were allowed to divide for a number of weeks) and on non-cancerous breast cells from women having BRCA1 mutations.

According to Park, changes in cell leading to cancer can be due to having only a single working copy of BRCA1. They believe that with this breakthrough they can explore other BRCA1 mutations, determine mutation’s cancer risk, and know the vulnerability of several BRCA1 mutations to anti-cancer medications.

 

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