Navigation Links
Genome analysis reveals new protein associated with breast cancer progression
Date:4/17/2008

A novel systems-based approach that combines comprehensive gene expression profiling with genome-wide transcription factor analysis and protein-protein interaction has led researchers to an important genetic marker that can help physicians know which breast cancer patients are at highest risk and will require more aggressive treatment, a research team based at the University of Chicago Medical Center reports in the April 15, 2008, issue of the journal Molecular Systems Biology.

The researchers found that high expression of a protein known as H2A.Z, which is associated with the expression of genes within the nucleus, can help physicians predict which patients are most at risk for disease spread and death. It could also serve as a new target for therapy.

Elevated H2A.Z expression is significantly associated with metastasis and shorter survival, and it could quickly help doctors make better predictions and treatment choices for their patients, said study director Kevin White, PhD, professor of human genetics and director of the Institute for Genomics and Systems Biology at the University of Chicago and Argonne National Laboratory. It could also provide clues to new therapies.

But, perhaps more important, he added, we think we have developed an integrated approach to genomic analysis that can be applied to a wide range of cancers.

Instead of a standard whole-genome analysis, looking for genetic variations that correlate with disease risk, White and colleagues integrated multiple genetic technologies to measure the effects of estrogens, which play a crucial role in many breast cancers, on multiple cellular pathways, what they refer to as a transcriptional regulatory cascade.

The female hormone estrogen acts by binding to the estrogen receptor, which carries the hormones signal to a cells nucleus, where it activates many other genes. One of those genes is a known cancer-related gene called c-MYC, which in turn regulates its own cascade of gene targets.

Whites team set out to map out the many sequential genetic events that occur in breast cancer cells after estrogen binding, using a series of innovative technologies. They ultimately found that estrogen-stimulated c-MYC enhanced production of H2A.Z, which altered the positioning and activation of various genes in ways that increased the odds that a cancer would spread to the lymph nodes and ultimately to distant sites, often resulting in the patients death.

This is not a simple process. In tumor cells from patients with estrogen-dependent breast cancers, the researchers found estrogen affected 1,615 genetic regions. One of those was the promoter for the gene for c-MYC, which, when activated, could bind another set of overlapping 311 genetic regions.

Both estrogen and c-MYC interact with the gene for H2A.Z, leading to increased production of this protein in breast cancer cells. When the researchers looked at tumor tissue samples collected from 500 patients, they found that elevated levels of H2A.Z were highly correlated with the spread of the cancer to lymph nodes and decreased patient survival. Adding H2A.Z expression to other known risk factors provided significant prognostic information, the authors note, beyond what these factors alone provide.

Although it has been implicated in genomic stability and gene transcription, H2A.Z has never been reported to be associated with cancer, said White. We would not have found this clinically important factor without taking such a large-scale integrated approach.

We suspect this integrated systems approach will lead us to a number of previously unsuspected genes that play a role in disease initiation and progression, he said. Many of these could become targets for new treatments.


'/>"/>

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

Related medicine news :

1. Open Biosystems Launches Decode RNAi Viral Screening Pools for Low-Cost Genome-Scale RNAi Screens
2. NTMir Announces First International Research Grant for Genome Sequencing
3. UCLA researchers examine human embryonic stem cell genome
4. Researchers urge ethics guidelines for human-genome research
5. Genome-wide association study on Parkinsons disease finds public home at NIH
6. Genomatix integrates genome-wide open chromatin from next generation sequencing
7. Genome-wide survey nets key melanoma gene
8. Project Will Map Genomes of 1,000 People Worldwide
9. International consortium announces the 1000 Genomes Project
10. Johns Hopkins to participate in 1000 Genomes Project
11. Evolution of human genomes guardian gives people unique protections from DNA damage
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:10/12/2017)... ... ... The American College of Medical Informatics (ACMI) will present the 2017 Morris ... of AMIA’s Annual Symposium in Washington, D.C. AMIA’s Annual Symposium is taking ... in the field of medical informatics, this prestigious award is presented to an individual ...
(Date:10/12/2017)... ... October 12, 2017 , ... Information about ... intend to develop to enable prevention of a major side effect of chemotherapy ... especially in pediatric patients. For cisplatin, hearing loss is FDA listed on-label as ...
(Date:10/12/2017)... , ... October 12, 2017 , ... HMP , ... recipient of a 2017 Folio Magazine Eddie Digital Award for ‘Best B-to-B Healthcare Website.’ ... on October 11, 2017. , The annual award competition recognizes editorial and design excellence ...
(Date:10/12/2017)... ... October 12, 2017 , ... On Saturday, October 21, the Health & ... by Moonlight to raise money for the American Heart Association Heart Walk. Teams of ... will work together to keep their treadmills moving for 5 hours. Treadmills will start ...
(Date:10/12/2017)... ... 2017 , ... Health Literacy Innovations (HLI), creator of the ... the Cancer Patient Education Network (CPEN), an independent professional organization that shares best ... alliance. , As CPEN’s strategic partner, HLI will help support CPEN members ...
Breaking Medicine News(10 mins):
(Date:10/2/2017)... , Oct. 2, 2017 The Rebound mobile app ... struggle to reverse the tide of prescription drug addiction. The ... their medicine intake and stepping down their dosage in a ... launch in December 2017; the first 100,000 people to sign ... at http://www.rebound-solution.com/ ...
(Date:9/25/2017)...   Montrium , an industry leader in ... IQPC Trial Master Files & Inspection Readiness Conference ... Clinical Services has selected eTMF Connect ... EastHORN, a leading European contract research organization (CRO), ... to enable greater collaboration with sponsors, improve compliance ...
(Date:9/19/2017)... venture-backed medical device company developing a non-invasive, robotically assisted, platform therapy that uses pulsed sound ... ... Jim Bertolina, PhD ... Tom Tefft ... device executive Josh Stopek , PhD, who has led R&D and business development teams ...
Breaking Medicine Technology: