Breast cancer is one of the most common cancers, affecting up to one in eight women during their lives in Europe, the UK and USA. Large population studies such as the Women’s Health Initiative and the Million Women Study have shown that synthetic sex hormones called progestins used in hormone replacement therapy, HRT, and in contraceptives can increase the risk of breast cancers.
Now medical researchers at the Institute of Molecular Biotechnology of the Austrian Academy of Sciences in Vienna have identified a key mechanism which allows these synthetic sex hormones to directly affect mammary cells.
The research builds on previous work by Prof Josef Penninger, the IMBA director, who found the first genetic evidence that a protein called RANKL is the master regulator of healthy bones. In a complex system that regulates bone mass, RANKL activates the cells that break down bone material when it needs to be replaced. When the system goes wrong and we make too much of the protein it triggers bone loss, leading to osteoporosis in millions of patients around the world every year. Finding exactly the same molecule in breast tissues led the scientists to the new link between sex hormones and breast cancer.
In a scientific article published on Nature’s website today, the research team show that a synthetic female sex hormone used in HRT and contraceptive pills can trigger RANKL in breast cells of mice. As a consequence, these mammary cells start to divide and multiply and fail to die when they should. Moreover, stem cells in the breast become able to renew themselves, ultimately resulting in breast cancer.
In a different set of mouse treatment tests, reported in a second Nature article also published today, researchers at Amgen have found that pharmacologic blocking of the RANKL system significantly delays mammary tumor formation leading to significantly fewer breast cancers in mice. In another mouse model, RANKL inhibition not only decreased breast tumor formation but also reduced lung metastasis.
“Ten years ago we formulated the hypothesis that RANKL might be involved in breast cancer and it took us a long time to develop systems to prove this idea”, says Prof Josef Penninger. ” I have to admit it completely surprised me just how massive the effects of the system were. Millions of women take progesterone derivatives in contraceptives and for hormonal replacement therapy. Since our results show that the RANKL system is an important molecular link between a synthetic sex hormone and breast tumors, one day women may be able to reduce their risk by taking blocking medicines in advance to prevent breast cancer”.
A monoclonal antibody, denosumab, that blocks RANKL has been recently approved in the US and the EU for the treatment of osteoporosis, and is currently under review for the treatment of bone metastases in patients with advanced cancer. “Further studies will be needed to prove the principle of our findings”, says Dr Daniel Schramek, who carried out the studies with Prof Josef Penninger at the Institute of Molecular Biotechnology in Vienna. “But we hope that medical trials using denosumab can be started in the near future to test whether the mouse studies can be directly translated to human breast cancer.”
This work was an international collaboration between lead researchers at IMBA and scientists at the Medical University of Vienna; the Garvan Institute of Medical Research, Sydney, Australia; the Ontario Cancer Institute, University of Toronto, Toronto, Canada; Harvard School of Public Health, Harvard Medical School and the Ragon Institute of MGH/MIT and Harvard, Boston, USA; the Institute for Genetics, Centre for Molecular Medicine (CMMC), and Cologne Excellence Cluster (CECAD), University of Cologne, Germany; University College London, UK; and the University of Erlangen-Nuremberg, Germany.
Notes to News Editors:
(1) A high quality copyright-free colour image of the human body showing breast cancer cell activation is available for free reproduction (with acknowledgement to IMBA) on request, or download directly from the website http:///www.imba.oeaw.ac.at/news-media/illustrations(2) RANK = Receptor Activator of Nuclear Factor ê B, this receptor is a membrane protein
RANKL = Receptor Activator of Nuclear Factor ê B Ligand, this is a chemical messenger which binds to RANK and activates it.
(3) Nature Advance Online Publication, Sept. 29, 2010, DOI 10.1038/nature09387. Title: Osteoclast differentiation factor RANKL controls development of progestin-driven mammary cancer (Schramek et al.)
See also DOI 10.1038/nature09495. Title: RANK Ligand is a Critical Mediator of Hormone and Carcinogen-Induced Mammary Epithelial Proliferation and Progression to Adenocarcinoma (Gonzalez-Suarez et al.)(4) About IMBA
For further information contact:Dr Heidemarie Hurtl, Communications, Institute of Molecular Biotechnology, Vienna
Dr. Heidemarie Hurtl | idw
Unique genome architectures after fertilisation in single-cell embryos
30.03.2017 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH
Transport of molecular motors into cilia
28.03.2017 | Aarhus University
The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.
To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
30.03.2017 | Health and Medicine
30.03.2017 | Health and Medicine
30.03.2017 | Medical Engineering