Source: Institute of Molecular Biotechnology | Summary: About one in eight women will develop invasive breast cancer over the course of her lifetime. Causes can be the use of synthetic sex hormones and other environmental factors, but also gene mutations like in the BRCA1 gene (BReast CAncer). US actress Angelina Jolie who underwent a preventive double mastectomy is the most famous carrier of a "faulty“ BRCA1 gene.On average, women with this mutation have an up to 87% lifetime risk of developing breast cancer. Tumors usually develop early in life. Until now, prophylactic surgery is the only procedure which significantly reduces the breast cancer risk, but which is also often associated with postoperative complications.
"In 2010, Josef Penninger, the scientific director of IMBA in Vienna and his team have shown that sex hormones can trigger breast cancer (Schramek et al., Nature) through proteins called RANKL and its receptor RANK, which are key factors in bone metabolism. RANKL and RANK also link sex hormones to breast cells by providing signals telling the breast cells to grow. This occurs normally in every woman during pregnancy and the menstruation cycle. However, if deregulated, mammary cells start to divide and multiply and fail to die when they should, ultimately resulting in breast cancer.
A multinational research effort now made the discovery that RANKL is also the main driver of BRCA1 mutation-driven breast cancer. In the current study, Verena Sigl, graduate student from Penninger's research group, showed that blocking the RANKL/RANK system in BRCA1 mutant mice led to largely normal mammary glands whereas invasive carcinomas could be found in the control group.
To determine the relevance of their results for humans, scientists in Vienna and Toronto isolated breast tissue cells from women who had undergone preventive mastectomy because of their BRCA1 mutation. In the human cell culture, too, RANKL inhibition led to a significant reduction of growth and spreading of breast tissue cells..."
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