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The researchers came to this discovery by identifying, for the first time, one of the molecular pathways that leads to the variety of breast cancer known as triple-negative. This cancer is more likely to affect younger women, and is most resistant to treatment. Scientists have known for some time that a malfunction of a tumor-suppressing gene known as BRCA1 can lead to the development of breast cancer. This gene is part of the cellular defense system by which the body ensures that any damaged DNA is not passed on to new cells, using mechanisms such as screening DNA for errors and sending cells carrying damaged DNA into hibernation or even programmed cell death. This is an important cancer-preventive role, because an accumulation of DNA damage can lead a cell to the out-of-control replication associated with cancerous tumors. BRCA1 plays a role in screening DNA and repairing double-strand breaks, a particularly dangerous form of damage. It also plays a role in verifying that DNA has been replicated and transferred properly to new cells. When BRCA1 fails, it may lead to the development of breast cancer, and often the particular variety that is negative for receptors of two hormones and a protein: estrogen, progesterone and HER2. Because such tumors are not dependent on these external factors for growth, they are harder to "starve" and kill. The vitamin D linkYet not all BRCA1-mutated cells turn into breast tumors. In a recent study, researchers determined that in the presence of another DNA repair factor known as 53BP1, BRCA1-deficient cells can still survive and reproduce in health. As 53BP1 levels decrease, the development of triple-negative tumors becomes more likely.In the new study, the researchers found that the loss of BRCA1 begins a chain of events in which a protein-degrading chemical is produced that starts to break down 53BP1. "It's a new pathway that explains how breast cancer cells lose 53BP1," lead researcher Susana Gonzalo said. Significantly, prior research has shown that in the presence of vitamin D, this chemical is less effective at degrading 53BP1. In the new study, they found that when BRCA1-deficient tumor cells were exposed to vitamin D, 53BP1 levels rose and proliferation slowed. This is a particularly important discovery because triple-negative breast cancers tend to be resistant to many of the most advanced cancer drugs, while the therapy that they are more likely to respond to - chemotherapy - carries potentially severe side effects. The researchers now believe that even in people who have already developed a drug-resistant, triple-negative cancer, vitamin D supplementation may actually render the tumors sensitive to drugs. Sources: http://www.sciencedaily.com/releases/2013/01/130122142911.htm http://phys.org |
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