Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Cancer researchers discover how BRCA1 mutation starts breast, ovarian cancers

16.07.2013
Scientists led by Drs. Mona Gauthier and Tak Mak at The Campbell Family Institute for Breast Cancer Research at the Princess Margaret Cancer Centre have solved a key piece in the puzzle of how BRCA1 gene mutations specifically predispose women to breast and ovarian cancers.

The answer, says Dr. Mak in research published today in the Journal of Experimental Medicine, is found in the way estrogen rushes in to "rescue" cells whose healthy functioning has been altered by oxidative stress, a well-established factor in cancer development.

Without estrogen, these damaged cells would die a natural death and not threaten the host in the long run, but with estrogen, these cells not only survive, but thrive and develop breast and ovarian cancers. In Canada, about 1,000 women die from BRCA1-related cancers every year.

The research published today illuminates the interplay between the tumour suppressor gene BRCA1 and a master regulator – Nrf2 – that governs the antioxidant response in cells. In healthy cells of all tissues, BRCA1 normally repairs damaged DNA in partnership with Nrf2, and so the cells are protected against oxidative stress. However, when the BRCA1 gene is mutated, it loses its ability to repair DNA and can no longer partner with Nrf2, shutting off its antioxidative function. In most tissues, the resulting oxidative stress kills the cells that have lost BRCA1 function.

However, in breast and ovary, the estrogen present in these tissues can swoop in to rescue BRCA1-deficient cells by triggering a partial turn-on of Nrf2. These unhealthy cells gain just enough resistance to oxidative stress to keep them alive and growing. Over time, these surviving BRCA1-deficient cells accumulate more and more mutations due to their lack of ability to repair DNA damage, eventually leading to the development of cancer in these tissues.

Dr. Mak likens the actions of Nrf2 to a ceiling sprinkler that puts out visible flames (oxidative stress) but doesn't reach the smoldering fire – cell damage – below.

He says: "Our research confirms that anti-estrogens can delay the onset of breast and ovarian cancers in carriers of BRCA1 mutations. Thus, the challenge is finding a way to block the antioxidant activity of estrogen without affecting its other activities that are necessary for female health. Modification of this one aspect of estrogen function would disrupt this significant cancer-initiating process while maintaining the positive effects of this hormone."

Dr. Gauthier and Dr. Mak discovered this critical interaction between BRCA1, Nrf2 and estrogen in initiating women's cancers by making use of genetically engineered mice. By examining the links between BRCA1 and oxidative stress in these mutant animals as well as in normal breast cells and breast tumours, they were able to generate results that finally explain why loss of a tumour suppressor gene normally active in all tissues leads only to breast and ovarian cancers. The missing piece of the puzzle was estrogen and its unexpected effects on the antioxidant regulation mediated by Nrf2.

Dr. Mak, Director of The Campbell Family Institute for Breast Cancer Research, is an internationally acclaimed immunologist renowned for his 1984 cloning of the genes encoding the human T cell receptor. He is also Professor, University of Toronto, in the Departments of Medical Biophysics and Immunology.

The research published today was funded by grants from the Canadian Institutes of Health Research, the Ontario Ministry of Health and Long-term Care, and The Princess Margaret Cancer Foundation.

About the Princess Margaret Cancer Centre, University Health Network

The Princess Margaret Cancer Centre and its research arm, the Ontario Cancer Institute – which includes The Campbell Family Cancer Research Institute – have achieved an international reputation as global leaders in the fight against cancer and delivering personalized cancer medicine. The Princess Margaret, one of the top five international cancer research centres, is a member of the University Health Network, which also includes Toronto General Hospital, Toronto Western Hospital and Toronto Rehabilitation Institute. All are research hospitals affiliated with the University of Toronto. For more information, go to http://www.theprincessmargaret.ca or http://www.uhn.ca

Jane Finlayson | EurekAlert!
Further information:
http://www.uhn.ca

More articles from Health and Medicine:

nachricht 'Living bandages': NUST MISIS scientists develop biocompatible anti-burn nanofibers
16.02.2018 | National University of Science and Technology MISIS

nachricht New process allows tailor-made malaria research
16.02.2018 | Eberhard Karls Universität Tübingen

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Demonstration of a single molecule piezoelectric effect

Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale

Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...

Im Focus: Hybrid optics bring color imaging using ultrathin metalenses into focus

For photographers and scientists, lenses are lifesavers. They reflect and refract light, making possible the imaging systems that drive discovery through the microscope and preserve history through cameras.

But today's glass-based lenses are bulky and resist miniaturization. Next-generation technologies, such as ultrathin cameras or tiny microscopes, require...

Im Focus: Stem cell divisions in the adult brain seen for the first time

Scientists from the University of Zurich have succeeded for the first time in tracking individual stem cells and their neuronal progeny over months within the intact adult brain. This study sheds light on how new neurons are produced throughout life.

The generation of new nerve cells was once thought to taper off at the end of embryonic development. However, recent research has shown that the adult brain...

Im Focus: Interference as a new method for cooling quantum devices

Theoretical physicists propose to use negative interference to control heat flow in quantum devices. Study published in Physical Review Letters

Quantum computer parts are sensitive and need to be cooled to very low temperatures. Their tiny size makes them particularly susceptible to a temperature...

Im Focus: Autonomous 3D scanner supports individual manufacturing processes

Let’s say the armrest is broken in your vintage car. As things stand, you would need a lot of luck and persistence to find the right spare part. But in the world of Industrie 4.0 and production with batch sizes of one, you can simply scan the armrest and print it out. This is made possible by the first ever 3D scanner capable of working autonomously and in real time. The autonomous scanning system will be on display at the Hannover Messe Preview on February 6 and at the Hannover Messe proper from April 23 to 27, 2018 (Hall 6, Booth A30).

Part of the charm of vintage cars is that they stopped making them long ago, so it is special when you do see one out on the roads. If something breaks or...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on High Temperature Shape Memory Alloys (HTSMAs)

15.02.2018 | Event News

Aachen DC Grid Summit 2018

13.02.2018 | Event News

How Global Climate Policy Can Learn from the Energy Transition

12.02.2018 | Event News

 
Latest News

Fingerprints of quantum entanglement

16.02.2018 | Information Technology

'Living bandages': NUST MISIS scientists develop biocompatible anti-burn nanofibers

16.02.2018 | Health and Medicine

Hubble sees Neptune's mysterious shrinking storm

16.02.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>