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
What happens in the cell nucleus after fertilization
06.12.2016 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
Researchers uncover protein-based “cancer signature”
05.12.2016 | Universität Basel
In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.
Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...
Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
06.12.2016 | Materials Sciences
06.12.2016 | Medical Engineering
06.12.2016 | Power and Electrical Engineering