Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

In those genetically predisposed, ’developmental reprogramming’ could explain cancer risk

31.05.2005


Researchers at The University of Texas M. D. Anderson Cancer Center may have uncovered the reason why some people who are genetically predisposed to hormone-dependent cancers develop the disease as an adult, while others who are similarly susceptible don’t.



In a study to be published on-line in the Proceedings of the National Academy of Sciences (PNAS) the week of May 30, 2005, they show, for the first time, that exposure to a pharmaceutical estrogen during fetal development can permanently "reprogram" tissue in a way that determines whether tumors will develop in adulthood.

While the study was conducted with rats that are susceptible to benign uterine tumors, and the compound used was diethylstilbestrol (DES), a banned estrogenic anti-miscarriage drug, the researchers say their conclusions likely have relevance for humans who inherit defective tumor suppressor genes that make them susceptible to a number of different cancers.


It could explain, for example, why some women who inherited BRCA1/2 gene defects develop breast cancer as adults while other women with the same genes remain disease-free, they say. "The kind of developmental reprogramming we see from this work could represent an important determinate of risk in people genetically susceptible to hormone-dependent tumors, such as uterine, breast and prostate cancer," says the study’s principal investigator, Cheryl Walker, Ph.D., a professor in the Department of Carcinogenesis. "It suggests that for gene-environmental interactions, the timing of the exposure may be critical, and it may happen much earlier than anyone ever suspected," she says.

While more work is needed to make the case that human cancer results in the same way, "we need to open our eyes to the notion that cancer that develops in adults may have been put in motion before a person is born," says the first author, Jennifer Cook, a graduate student who works with Walker at M. D. Anderson’s Science Park Research Division in Smithville, Texas.

The study was designed to challenge the longstanding notion that cancer arises when susceptible individuals are exposed to cancer-triggering compounds or events over the span of their lifetime. To test whether estrogen, found in both the environment and in some drugs, could reprogram tissue early, Walker, Cook and their team designed a study using female rats that are genetically predisposed to development of uterine leiomyoma, the same kind of benign fibroid tumors that many women have. Typically, 65 percent of rats carrying this genetic defect develop the tumors as an adult, and a set of these animals were used as a "control" group.

For the experimental group, researchers used another set of genetically susceptible rats and exposed them to DES, which is highly estrogenic, 3-5 days after they were born - a crucial period in the development of their reproductive tract.

They found that by the time they reached adulthood (16 months), virtually all of the rats in the experimental group had developed leiomyoma, and the tumors were larger and more numerous than in the control group. In contrast, none of the DES-exposed rats that lacked the genetic defect developed tumors by 16 months.

"The DNA of DES-exposed animals had been modified by DES in a way that changed how genes responded to estrogen, causing this tissue to be hypersensitive to the effects of this hormone," Walker says.

The researchers theorize that DES had permanently altered the rat’s normal response to estrogen, a "reprogramming" of the normal physiological responses to estrogen, which led to cancer when the animal had an inherited genetic defect. In that way, DES had changed the "penetrance," or likelihood of causing cancer, of the faulty tumor suppressor gene.

Nancy Jensen | EurekAlert!
Further information:
http://www.mdanderson.org

More articles from Life Sciences:

nachricht Seeing on the Quick: New Insights into Active Vision in the Brain
15.08.2018 | Eberhard Karls Universität Tübingen

nachricht New Approach to Treating Chronic Itch
15.08.2018 | Universität Zürich

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Unraveling the nature of 'whistlers' from space in the lab

A new study sheds light on how ultralow frequency radio waves and plasmas interact

Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...

Im Focus: New interactive machine learning tool makes car designs more aerodynamic

Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.

When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.

Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....

Im Focus: The “TRiC” to folding actin

Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.

Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...

Im Focus: Lining up surprising behaviors of superconductor with one of the world's strongest magnets

Scientists have discovered that the electrical resistance of a copper-oxide compound depends on the magnetic field in a very unusual way -- a finding that could help direct the search for materials that can perfectly conduct electricity at room temperatur

What happens when really powerful magnets--capable of producing magnetic fields nearly two million times stronger than Earth's--are applied to materials that...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

2018 Work Research Conference

25.07.2018 | Event News

 
Latest News

Unraveling the nature of 'whistlers' from space in the lab

15.08.2018 | Physics and Astronomy

Diving robots find Antarctic winter seas exhale surprising amounts of carbon dioxide

15.08.2018 | Earth Sciences

Early opaque universe linked to galaxy scarcity

15.08.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>