Navigation Links
Enhanced DNA-repair mechanism can cause breast cancer
Date:10/14/2007

Although defects in the "breast cancer gene," BRCA1, have been known for years to increase the risk for breast cancer, exactly how it can lead to tumor growth has remained a mystery. In the October 15, 2007, issue of the journal Cancer Research, scientists from the University of Chicago and Kyoto University, Japan, suggest that a mechanism that normally repairs damaged DNA may function abnormally in BRCA1 carriers leading to one type of poor-prognosis breast cancer.

Their findings provide insight into how the normal BRCA1 gene suppresses the growth of tumors as well as the nature of the genetic instability that leads to cancer when BRCA1 is defective.

"If you take a normal, healthy cell and get rid of BRCA1, you end up with an unhealthy, slow-growing cell," said Douglas Bishop, PhD, associate professor of radiation and cellular oncology at Chicago and principal investigator of the study. "Thats a bit of a paradox, because loss of BRCA1 also causes tumors and tumor formation is not normally associated with poor cell growth."

Bishop and colleagues found that the slow growth caused by loss of BRCA1 could be compensated for by increasing the amount of the DNA repair protein RAD51.

RAD51 is involved in homologous recombination, a method used by cells to repair damaged DNA. In homologous recombination, organisms heal broken chromosomes using an unbroken chromosome copy as a template.

BRCA1 itself promotes DNA repair through recombination and the conventional view is that loss of BRCA1 causes tumors because DNA repair fails. The new work from Bishop and colleagues challenges this view.

"BRCA1-deficiency by itself would probably not cause a tumor," Bishop said, "but cells that manage to compensate for the BRCA1 defect in repair by ramping up RAD51 levels are likely to be less genetically stable than normal cells and therefore more prone to form tumors."

Using a public database, Bishop and colleagues examined genomic data from 117 primary breast tumors for evidence of elevated levels of RNAs for genes involved in homologous recombination. They found that the level of RNA for three genes -- RAD51 and two of its key accessory factors -- was significantly higher in BRCA1-deficient tumors compared with breast tumors that were not associated with BRCA1 mutations.

"High levels of RAD51 may help cells that lack BRCA1 overcome the defects in recombination caused by loss of BRCA1," Bishop said, "but the recombination that occurs in this situation may be abnormal and may actually cause mutations which in turn lead to the development of a tumor."

When the researchers took normal, healthy cells in culture and disabled the BRCA1 gene, the cells survived, but grew slowly and were unable to repair DNA damage normally. When Bishop and his coworkers increased the amount of RAD51 in these cells, however, the ability of cells to repair DNA damage was restored and the mutated cells grew more quickly.

In the future "it will be interesting to determine whether high levels of RAD51 can predict tumor prognosis," said Bishop. "Its also possible that tumor cells with high levels of RAD51 are particularly dependent on that gene for survival and therefore sensitive to drugs that target RAD51"


'/>"/>

Contact: John Easton
john.easton@uchospitals.edu
773-702-6241
University of Chicago Medical Center
Source:Eurekalert

Related biology news :

1. Mouse with designer liver has enhanced glucose tolerance, insulin response
2. Study finds that nutritionally enhanced rice reduces iron deficiency
3. Researchers report technique for freezing and preserving genetically enhanced pig embryos
4. Fish growth changes enhanced by climate change
5. Making mice with enhanced color vision
6. Scientists genetically engineer tomatoes with enhanced folate content
7. A new mechanism of regulating RNA degradation
8. Plants, animals share molecular growth mechanisms
9. PET/MRI scans may help unravel mechanisms of prenatal drug damage
10. Researchers discover molecular mechanism that desensitizes us to cold
11. Chemists identify immune system mechanism for methamphetamine binges
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/2/2017)... , Feb. 1, 2017  Central to its ... meaningful advances worldwide, The Japan Prize Foundation today ... who have pushed the envelope in their respective ... Communication. Three scientists are being recognized with the ... that not only contribute to the advancement of ...
(Date:1/30/2017)...   Invitae Corporation (NYSE: NVTA ... today announced that it will report its fourth quarter ... on Monday, February 13, 2017, and Invitae,s management team ... p.m. Eastern / 1:45 p.m. Pacific. ... financial results, guidance, and recent developments and will spend ...
(Date:1/25/2017)... Jan. 25, 2017 The Elements of Enterprise ... lifecycle is comprised of a comprehensive set of ... of maintaining digital identities and providing a secured ... There are significant number of programs opted by ... time by optimizing processes and changing policies. However, ...
Breaking Biology News(10 mins):
(Date:2/16/2017)... ANGELES , Feb. 16, 2017   ... ), a clinical-stage biotechnology company developing first-in-class biological ... announced that it has elected to terminate its ... natriuretic peptide receptor agonists, including Cenderitide. ... strategic move as we prioritize our efforts to ...
(Date:2/16/2017)...  Champions Oncology, Inc. (NASDAQ: CSBR ), ... advanced technology solutions and products to personalize the development ... of new cohorts of PDX models to their existing ... Champions, product line in hepatocellular cancer, breast cancer, castrate ... non-small cell lung cancer (including EGFR mutation; ALK/ROS1 positive) ...
(Date:2/16/2017)... ... February 16, 2017 , ... ... Research Inc. has further extended its industry leading Biochemistry Services specifically targeting ... state-of-the-art cGMP techniques and methods for the biochemical and biosimilar characterization ...
(Date:2/15/2017)... WASHINGTON, Feb. 15, 2017  Vanda Pharmaceuticals Inc. ... results for the fourth quarter and full year ... an exceptional year for Vanda as we continued ... and secured long-term exclusivity for Fanapt," said Mihael ... addition, our emerging pipeline with important 2017 milestones ...
Breaking Biology Technology: