Navigation Links
Breast cancer cells regulate multiple genes in response to estrogen-like compounds
Date:7/19/2010

COLUMBUS, Ohio Cancer researchers have discovered a previously unknown type of gene regulation and DNA behavior in breast cancer cells that may lead to better insight about environmental exposure to estrogen-like compounds.

A new study, published in the journal Genome Research by researchers at The Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC-James), provides the first evidence that cells can regulate many genes at once by looping their DNA, contributing to cancer when it goes awry. In this study, the gene regulation was discovered in breast cancer cells as a response to the hormone estrogen and resulted in the silencing of 14 genes at one time.

Tim H.-M. Huang, professor of molecular virology, immunology and medical genetics in the OSUCCC-James human cancer genetics program, and Pei-Yin Hsu, a visiting scholar and researcher in Huang's lab, discovered the DNA looping event in a breast cancer cell line gene cluster at chromosome region 16p11.2. They validated the finding using normal human breast epithelial cells and two animal models.

In addition, they used the normal-cell model to determine if long-term exposure to nine estrogen-like chemicals can initiate gene silencing through this mechanism. These chemicals included diethylstilbestrol, two thalates and bisphenol A (BPA).

The suppressive effects varied in normal cells. When the investigators exposed a group of four rats to BPA for 21 days, however, they found concurrent suppression of ten genes comparable to those located at 16p11.2. These findings, says Huang, suggest that continuous exposure to estrogen-like compounds might lead to permanent silencing of genes located in this conserved cluster.

In healthy breast epithelial cells, 14 gene regulatory sites came together to form a single, temporary transcription site, Huang says. "But in breast cancer cells, there is no coordinated transcription site pairing, the DNA loops become tangled and the entire gene complex shuts down in a dead knot." (For a demonstration of DNA looping, go to http://www.youtube.com/watch?v=4y0e6oumqdo.)

In some cases, Huang says, this multi-gene regulatory mechanism can increase gene expression and oncogenic activity, and further contribute to cancer development.

"We offer a new concept in this paper for the collective regulation of gene transcription," says first author Hsu, who identified the loop structures and their significance. "We found that in normal breast cells, DNA looping is more flexible and brings different promoters together temporarily. But in cancer, this complex just locks up and causes long-term suppression."

Researchers generally believe that transcription factors bind to a site on a single gene, and then the gene is actively transcribed, according to Huang. The study's findings show that this is not always the case. Sometimes the promoter is located far away, and it is remotely controlled.

"Overall, our study shows that certain regions of the genome are silenced because the DNA has lost flexibility, and that this inflexible DNA status might be a good marker for studying environmental exposure to estrogen-like compounds," Hsu says.


'/>"/>

Contact: Darrell E. Ward
Darrell.Ward@osumc.edu
614-293-3737
Ohio State University Medical Center
Source:Eurekalert

Related medicine news :

1. Susan G. Komen awards Case Western Reserve nearly $500,000 to study breast cancer in older women
2. Prediction tool helps estimate local recurrence in patients with noninvasive breast cancer
3. Experts Issue New Guidelines on Breast Cancer Drugs
4. Radiation device allows for targeted breast radiation to control cancer
5. Scientists reprogram triple-negative breast cancer cells to respond to tamoxifen
6. Fish Oil Supplements Linked to Lower Risk of Breast Cancer: Study
7. Mathematical models for breast cancer detection with microwave tomography are cheaper and less risky
8. Breast, Colon Cancer Screening Rates High, But Not High Enough
9. Scientists find link between estrogen metabolism pathway and breast cancer risk
10. Revolutionary therapy slows tumor growth in advanced breast cancer, Penn research reports
11. A key mechanism links virgin olive oil to protection against breast cancer
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/24/2016)... ... , ... June 19, 2016 is World Sickle Cell Observance Day. In an ... of holistic treatments, Serenity Recovery Center of Marne, Michigan, has issued a ... Cell Disease (SCD) is a disorder of the red blood cells, which can cause ...
(Date:6/24/2016)... Fla. (PRWEB) , ... June 24, 2016 , ... Global ... Trend magazine’s 2016 Legal Elite. The attorneys chosen by their peers for this recognition ... Florida. , Seven Greenberg Traurig Shareholders received special honors as members of this year’s ...
(Date:6/24/2016)... ... ... of Topricin and MyPainAway Pain Relief Products, join The ‘Business for a Fair Minimum Wage’ ... 2020 and then adjusting it yearly to increase at the same rate as the median ... floor does not erode again, and make future increases more predictable. , The company is ...
(Date:6/24/2016)... (PRWEB) , ... June 24, 2016 , ... ... Living, is proud to recognize Dr. Barry M. Weintraub as a prominent plastic ... most beautiful women in the world, and the most handsome men, look naturally ...
(Date:6/24/2016)... ... ... National recruitment firm Slone Partners is pleased to announce the placement of ... President of North American Capital Sales at HTG Molecular . , ... the commercialization of the HTG EdgeSeq system and associated reagents in North America. , ...
Breaking Medicine News(10 mins):
(Date:6/23/2016)... Roche (SIX: RO, ROG; OTCQX: RHHBY) announced ... BRAHMS PCT (procalcitonin) assay as a dedicated testing solution ... this clearance, Roche is the first IVD company in ... sepsis risk assessment and management. PCT is ... levels in blood can aid clinicians in assessing the ...
(Date:6/23/2016)... 2016 Capricor Therapeutics, Inc. ... biotechnology company focused on the discovery, development and ... enrollment in its ongoing randomized HOPE-Duchenne clinical trial ... of its 24-patient target. Capricor expects the trial ... of 2016, and to report top line data ...
(Date:6/23/2016)... -- Bracket , a leading clinical trial technology and ... platform, Bracket eCOA (SM) 6.0, at the 52 nd ... 2016 in Philadelphia , Pennsylvania.  A demonstration ... of its kind to fully integrate with RTSM, will be ... is a flexible platform for electronic clinical outcomes assessments that ...
Breaking Medicine Technology: