Navigation Links
Slight changes in 2 key genes appear to launch breast cancer development

Washington, DC Researchers at Georgetown Lombard Comprehensive Cancer Center have been able to show, in mice, how just a little adjustment in the expression of two common genes can promote the kind of cellular changes that led to breast cancer. They say these tweaks likely mimic natural variation women have in expression of the two genes.

In the May 15 issue of Cancer Research published online today, the scientists say that a readout of these two genes estrogen receptor alpha and p53 in healthy women could provide an "interacting biomarker" that might predict future breast cancer risk.

"It was believed that both of these genes only act once breast cancer had developed p53 mutations are found in many cancers, including breast cancer, and the majority of women with breast cancer have over-expression of this common estrogen receptor," says the study's lead investigator, Priscilla A. Furth, MD, a professor of oncology and medicine with Lombardi at Georgetown University Medical Center. "What wasn't known is that different levels of expression of these genes can help launch the cellular changes that lead to breast cancer.

"That suggests that testing women for their own variations in these genes might potentially give us a clue as to which women are at higher risk for development of breast cancer," Furth says.

The first author of the study is Edgar S. Daz-Cruz, Ph.D., a fellow at Lombardi supported by a Susan G. Komen for the Cure Postdoctoral Fellowship.

One focus of Furth's lab is to eventually develop a panel of tests that will accurately determine an individual woman's future risk of developing breast cancer so that counseling and monitoring can be tailored to each patient. To find the genes and proteins that carry such risk, she has developed unique mouse models in which she can manipulate various genetic factors to see how breast cancer risk changes over time.

In this study, Daz-Cruz and Furth developed mice in which one copy of the p53 gene was silenced (mice, and humans, inherit two copies, one from each parent), and tested the effect on what is known as development of preneoplasia, or early breast cancer progression. The p53 gene, long called the "guardian of the genome," is known as a very powerful tumor suppressor because it regulates cell growth. Alterations to p53 are reported in 30-40 percent of human breast cancers, and this loss is linked to increased cancer aggressiveness, poor prognosis, and chemotherapy resistance.

The researchers also increased expression of the estrogen receptor by two-fold, an equivalent elevation sometimes seen in women. Almost 70 percent of women with breast cancer have estrogen receptorpositive breast cancer, meaning that the estrogen hormone is driving cell growth because it is binding to, in some cases, an over abundance of its receptors on the outside of breast cells.

Both mouse models showed significant precancerous changes in breast tissue.

They then compared those effects with changes seen in mice that had one p53 gene as well as twice as much estrogen receptor expression, and found substantially higher evidence of early stage breast cancer progression.

"Normal breast tissue functioning requires a balance of cell growth and cell death, and in this study we found that both deregulated estrogen receptor function and p53 expression independently, and in combination, altering this balance and transforming cells," Furth says.

Furth says that both tweaks in gene expression levels were relatively minor, and that she was sobered to find that they had such an effect on otherwise healthy breast tissue. "We increased ER expression, but in a way that could be found in normal variation among women," she says. "And the mice lost one of their two p53 genes, but loss of that single copy only decreases but does not eliminate expression.

"These are not the only two molecules that are responsible for breast cancer development, but they are important and they can potentially provide us with an early warning or even with prevention strategies," Furth says.


Contact: Karen Mallet
Georgetown University Medical Center

Related biology news :

1. Study finds women slightly more likely to die than men in the 30 days following a heart attack
2. Home tooth bleaching slightly reduces enamel strength
3. Slight changes in climate may trigger abrupt ecosystem responses
4. Chesapeake Bay ecosystem health remains poor, but slightly improved in 2007
5. Subtle changes in PTEN tumor suppressor gene can determine cancer susceptibility
6. Lifestyle changes for teens critical in light of research about teens heart disease risk
7. Multiple sclerosis risk changes with the season
8. Small changes in protein chemistry play large role in Huntingtons disease
9. Nanoscale changes in collagen are a tipoff to bone health
10. Genomes of identical twins reveal epigenetic changes that may play role in lupus
11. Lifestyle changes may stave off diabetes for a decade
Post Your Comments:
(Date:11/26/2015)... , Nov. 26, 2015 Research and ... the "Capacitive Fingerprint Sensors - Technology and Patent ... --> --> Fingerprint ... especially in smartphones. The fingerprint sensor vendor Idex forecasts ... sensor units in mobile devices and of the fingerprint ...
(Date:11/20/2015)... NXTD ) ("NXT-ID" or the ... mobile commerce market and creator of the Wocket® smart ... recently interviewed on The RedChip Money Report ... on Bloomberg Europe , Bloomberg Asia, Bloomberg Australia, ... NXTD ) ("NXT-ID" or the "Company"), a biometric authentication ...
(Date:11/19/2015)... Calif. , Nov. 19, 2015  Based on ... Frost & Sullivan recognizes BIO-key with the 2015 Global ... Each year, Frost & Sullivan presents this award to ... line catering to the needs of the market it ... product line meets and expands on customer base demands, ...
Breaking Biology News(10 mins):
(Date:11/25/2015)... , Nov. 25, 2015  PharmAthene, Inc. (NYSE ... has adopted a stockholder rights plan (Rights Plan) in ... operating loss carryforwards (NOLs) under Section 382 of the ... --> PharmAthene,s use of its NOLs could ... change" as defined in Section 382 of the Code. ...
(Date:11/25/2015)... /PRNewswire/ - Aeterna Zentaris Inc. (NASDAQ:  AEZS; TSX: AEZ) ... remain fundamentally strong and highlights the following developments: ... DSMB recommendation to continue the ZoptEC Phase 3 ... final interim efficacy and safety data , ... with heavily pretreated castration- and Taxane-resistant prostate cancer ...
(Date:11/24/2015)... , Nov. 24, 2015  Asia-Pacific (APAC) ... research organisation (CRO) market. The trend of outsourcing ... lower margins but higher volume share for the ... and scale, however, margins in the CRO industry ... (CRO) Market ( ), finds that ...
(Date:11/24/2015)... ... November 24, 2015 , ... Copper ... unless it is bound to proteins, copper is also toxic to cells. With ... Worcester Polytechnic Institute (WPI) will conduct a systematic study of copper in the ...
Breaking Biology Technology: