Navigation Links
Cancer researchers discover how BRCA1 mutation starts breast, ovarian cancers
Date:7/15/2013

(TORONTO, Canada July 15, 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.


'/>"/>

Contact: Jane Finlayson
jane.finlayson@uhn.ca
416-946-2846
University Health Network
Source:Eurekalert

Related medicine news :

1. Notre Dame researchers offer new insights on cancer cell signaling
2. Rancid Fish Oil Capsules May Partly Explain Omega-3 and Prostate Cancer Findings, Suggest Co-founders of Omega3 Innovations
3. Januvia Pancreatic Cancer Lawsuit: Bernstein Liebhard LLP Comments on Growing Litigation Surrounding Januvia
4. NFL Kicking Great Morten Andersen Joins Kicking For The Dream’s Effort to Fight Ovarian Cancer
5. Actos Bladder Cancer Lawsuit News: Bernstein Liebhard LLP Comments on India Regulatory Agency Decision to Ban Actos
6. Arena Football League (AFL) Kicker Carlos Martinez Joins Kicking for the Dream’s Effort to Fight Ovarian Cancer
7. Global Breast Cancer Market 2013: Latest Industry Analysis, Size, Share, Growth, Trends and Forecast Research Report Available at Marketresearchreports.biz
8. Study finds strong pregnancy outcomes for survivors of childhood cancer
9. Lurie Cancer Center given outstanding rating
10. Research finds racial/ethnic disparities in health care among older male cancer survivors
11. Damon Runyon, Sohn Conference Foundations name 4 new pediatric cancer research fellows
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/9/2016)... ... February 09, 2016 , ... Sir ... company , is proud to announce that many of their franchises have received ... service. The hard surface restoration franchises received customer recognition through positive reviews and ...
(Date:2/8/2016)... (PRWEB) , ... February 08, 2016 , ... CURE ... patients, has officially launched the Multiple Myeloma Heroes Awards event , which will ... in the lives of patients with MM. The MM Heroes Awards nomination process ...
(Date:2/8/2016)... ... 08, 2016 , ... Stephanie Hebert Insurance Agency, serving families ... new charity campaign. As part of their ongoing community involvement program, funds are ... that children deserve a voice, and in the spirit of neighbors helping neighbors ...
(Date:2/8/2016)... ... February 08, 2016 , ... If you are feeling that your clothes are ... alone. According to the Center for Disease Control and Prevention (CDC), 34.9% of U.S. ... certain types of cancer, some of the leading causes of preventable death. February ...
(Date:2/8/2016)... ... February 08, 2016 , ... Local insurance agency ... Venice, FL area, has initiated a fundraiser for a two year old little ... days after Christmas. To support this beautiful child who is facing life’s journey ...
Breaking Medicine News(10 mins):
(Date:2/9/2016)... 2016 Mast Therapeutics, Inc. (NYSE MKT: ... cell disease and heart failure, today announced that it intends ... common stock in an underwritten public offering.  The offering is ... no assurance as to whether or when the offering may ... of the offering.   --> ...
(Date:2/9/2016)... The global prefilled syringes market accounted for ... to grow with a CAGR of 12.9% during 2015-2020. ... dominated the global prefilled syringes market, with 90.1% share ... The global market of prefilled syringes is up ... population, increasing demand for vaccines, increasing prevalence of chronic ...
(Date:2/9/2016)... The life of Dr. Jan Vilcek , celebrated immunologist ...  Twists of fate, combined with sheer grit, brought him from ... communist Czechoslovakia to New York City ... history by playing a key role in the development of ...  Dr. Vilcek brings readers along his improbable journey in his ...
Breaking Medicine Technology: