Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Novel breast cancer gene found

09.01.2015

BCL11A is active in difficult-to-treat triple-negative breast cancer

A new study identifies a gene that is especially active in aggressive subtypes of breast cancer. The research suggests that an overactive BCL11A gene drives triple-negative breast cancer development and progression.

The research, which was done in human cells and in mice, provides new routes to explore targeted treatments for this aggressive tumour type.

There are many types of breast cancers that respond differently to treatments and have different prognoses. Approximately one in five patients is affected by triple-negative breast cancer; these cancers lack three receptor proteins that respond to hormone therapies used for other subtypes of breast cancer. In recent years it has become apparent that the majority of triple-negative tumours are of the basal-like subtype.

Although new treatments are being explored, the prognosis for triple-negative cancer is poorer than for other types. To date, only a handful of genomic aberrations in genes have been associated with the development of triple-negative breast cancer.

The team looked at breast cancers from almost 3000 patients. Their search had a particular focus: they examined changes to genes that affect the behaviour of stem cells and developing tissues, because other work they have done suggests that such genes, when mutated, can often drive cancer development. Among these was BCL11A.

"Our understanding of genes that drive stem cell development led us to search for consequences when these genes go wrong," says Dr Pentao Liu, senior author on the study, from the Wellcome Trust Sanger Institute. "BCL11A activity stood out because it is so active in triple-negative cancers.

"It had all the hallmarks of a novel breast cancer gene."

Higher activity of the BCL11A gene was found in approximately eight out of ten patients with basal-like breast cancer and was associated with a more advanced grade of tumour. In cases where additional copies of the BCL11A gene were created in the cancer, the prospects for survival of the patient were diminished.

"Our gene studies in human cells clearly marked BCL11A as a novel driver for triple-negative breast cancers," says Dr Walid Khaled, joint first author on the study from the Wellcome Trust Sanger Institute and University of Cambridge. "We also showed that adding an active human BCL11A gene to human or mouse breast cells in the lab drove them to behave as cancer cells.

"As important, when we reduced the activity of BCL11A in three samples of human triple-negative breast cancer cells, they lost some characteristics of cancer cells and became less tumorigenic when tested in mice. So by increasing BCL11A activity we increase cancer-like behaviour; by reducing it, we reduce cancer-like behaviour."

When BCL11A was inactivated in an experimental system in mice, no mice developed tumours in the mammary gland, whereas all untreated animals developed tumours.

The team also showed that BCL11A is required for normal development of breast stem cells and progenitors, which are thought to be the cells that, when mutated, give rise to basal-like breast cancer.

"This exciting result identifies a novel breast cancer gene in some of the more difficult-to-treat cases," says Professor Carlos Caldas, Professor of Cancer Medicine and Director of the Cambridge Breast Cancer Research Unit at the University of Cambridge, and Head of Breast Cancer Functional Genomics at Cancer Research UK Cambridge Institute. "It builds on our work to develop a comprehensive molecular understanding of breast cancer that will inform clinical decisions and treatment choices.

"Finding a novel gene that is active in cancer should also help in the search for new treatments."

The team propose that BCL11A is a strong candidate for development of a possible targeted treatment.

Publication Details

Khaled, WT, Lee SC et al. (2015) BLC11A is a triple-negative breast cancer gene with critical functions in stem and progenitor cells. Nature Communications, published online in advance of print publication doi: 10.1038/ncomms6987

Funding

This work was supported by the Wellcome Trust and the Wellcome Trust Sanger Institute. Authors were supported by individual funding from BBSRC, King's College, Cambridge, Cancer Research UK, Hutchinson Whampoa Ltd. and Medical Research Council.

Participating Centres

  • Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK
  • Department of Pathology, University of Cambridge, Cambridge, UK
  • Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Cambridge, UK
  • Department of Oncology, University of Cambridge, Cambridge, UK
  • SAIC-Frederic, National Cancer Institute-Frederick, Frederick, MD, USA
  • The Methodist Hospital Research Institute, 6670 Bertner Street, Houston, TX, USA
  • Addenbrooke's Hospital, Cambridge University Hospital NHS Foundation Trust and NIHR Cambridge Biomedical Research Centre, Cambridge, UK
  • Cambridge Experimental Cancer Medicine Centre, Cambridge, UK
  • Department of Pharmacology, University of Cambridge, Cambridge, UK
  • Molecular Oncology Department, BC Cancer Agency Research Centre, Vancouver, BC, Canada

Selected Websites

Cancer Research UK is the world's leading cancer charity dedicated to saving lives through research. The charity's pioneering work into the prevention, diagnosis and treatment of cancer has helped save millions of lives. It receives no government funding for its life-saving research. Every step it makes towards beating cancer relies on every pound donated. Cancer Research UK has been at the heart of the progress that has already seen survival rates in the UK double in the last forty years. Today, 2 in 4 people survive cancer. Cancer Research UK's ambition is to accelerate progress so that 3 in 4 people will survive cancer within the next 20 years. It supports research into all aspects of cancer through the work of over 4,000 scientists, doctors and nurses. Together with its partners and supporters, the charity's vision is to bring forward the day when all cancers are cured.
http://www.cancerresearchuk.org/

The Wellcome Trust Sanger Institute is one of the world's leading genome centres. Through its ability to conduct research at scale, it is able to engage in bold and long-term exploratory projects that are designed to influence and empower medical science globally. Institute research findings, generated through its own research programmes and through its leading role in international consortia, are being used to develop new diagnostics and treatments for human disease.
http://www.sanger.ac.uk

The Wellcome Trust is a global charitable foundation dedicated to achieving extraordinary improvements in human and animal health. We support the brightest minds in biomedical research and the medical humanities. Our breadth of support includes public engagement, education and the application of research to improve health. We are independent of both political and commercial interests.
http://www.wellcome.ac.uk

Mark Thomson | EurekAlert!

More articles from Life Sciences:

nachricht One step closer to reality
20.04.2018 | Max-Planck-Institut für Entwicklungsbiologie

nachricht The dark side of cichlid fish: from cannibal to caregiver
20.04.2018 | Veterinärmedizinische Universität Wien

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Spider silk key to new bone-fixing composite

University of Connecticut researchers have created a biodegradable composite made of silk fibers that can be used to repair broken load-bearing bones without the complications sometimes presented by other materials.

Repairing major load-bearing bones such as those in the leg can be a long and uncomfortable process.

Im Focus: Writing and deleting magnets with lasers

Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.

Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...

Im Focus: Gamma-ray flashes from plasma filaments

Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.

The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...

Im Focus: Basel researchers succeed in cultivating cartilage from stem cells

Stable joint cartilage can be produced from adult stem cells originating from bone marrow. This is made possible by inducing specific molecular processes occurring during embryonic cartilage formation, as researchers from the University and University Hospital of Basel report in the scientific journal PNAS.

Certain mesenchymal stem/stromal cells from the bone marrow of adults are considered extremely promising for skeletal tissue regeneration. These adult stem...

Im Focus: Like a wedge in a hinge

Researchers lay groundwork to tailor drugs for new targets in cancer therapy

In the fight against cancer, scientists are developing new drugs to hit tumor cells at so far unused weak points. Such a “sore spot” is the protein complex...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

IWOLIA: A conference bringing together German Industrie 4.0 and French Industrie du Futur

09.04.2018 | Event News

 
Latest News

Magnetic nano-imaging on a table top

20.04.2018 | Physics and Astronomy

Start of work for the world's largest electric truck

20.04.2018 | Interdisciplinary Research

Atoms may hum a tune from grand cosmic symphony

20.04.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>