Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

In breast cancer metastasis, researchers identify possible drug target

28.01.2013
The spread of breast cancer to distant organs within the body, an event that often leads to death, appears in many cases to involve the loss of a key protein, according to UC San Francisco researchers, whose new discoveries point to possible targets for therapy.

In the January 27, 2013 online edition of Nature Cell Biology, UCSF scientists describe for the first time how the protein, known as GATA3 — which is abnormal or absent in many cases of human breast cancer — normally acts downstream in biochemical pathways to prevent the distant spread of cancer, an event called metastasis.

The discovery points to a biochemical control point that simultaneously holds in check several key events required for tumor cells to successfully spread.

"When GATA3 is present, it turns off many genes that are active in metastasis," said Zena Werb, PhD, a UCSF professor of anatomy who led the research. "We now have identified the molecular mechanisms involved."

The key finding of the new study is that GATA3 acts downstream biochemically to activate a molecule — obscure until now — called microRNA29b. MicroRNA29b in turn stops protein production from other genes that play vital roles in metastasis.

The absence or loss of GATA3 can free cancerous cells to break free from their defined roles and tethers within a tumor, to move away from the tumor mass, to induce cancer-promoting inflammation, and to stimulate the development of new blood vessels that can help spreading cancerous cells regrow as tumors in new locations.

"People knew that some of these genes were turned on in some cancers, but they did not know they were turned on because GATA3 and microRNA29b were turned off," Werb said. "If you have 20 genes that are becoming less active all at once due to microRNA29b, it could have a profound effect."

Working with mice, the researchers found that restoring microRNA29b to one of the most deadly types of breast cancer stopped metastasis. But the researchers also found that if they knocked out the microRNA29b, tumors spread even in the presence of GATA3, suggesting that microRNA29b can be the driver of metastasis.

In the mouse models of breast cancer studied by Werb's team, GATA3 normally restrains cancerous cells from breaking away from the main tumor and migrating to other organs.

It might be possible, Werb said, to develop drugs that inhibit breast cancer metastasis by re-activating these controls in cancerous cells that have lost the normal protein.

Many researchers who study early stages of cancer focus on abnormal genes and proteins that cause cells to expand their numbers rapidly, a hallmark of cancer.

However, the ability to spread to distant places and to eventually cause lethal complications requires not only cell division and tumor growth, but also changes in how the cancerous cell negotiates with its surroundings. This relationship must be altered to permit cancer to spread, according to earlier research findings by Werb and others.

"Many of the key processes in cancer that GATA3 suppresses take place outside the cell, in the surrounding environment," she said.

GATA3 is a master control for luminal cells, which line the milk-carrying ducts of the breast. In essence, GATA3 dictates the defining characteristics of a normal breast cell, Werb said.

Luminal breast cancers are the most common form of the disease, and the hormones estrogen and progesterone drive their growth. Loss of the normal GATA3 protein as luminal breast cancers evolve is associated with a greater risk of death, Werb said, and occurs in roughly 10 percent of luminal breast cancer cases.

But, along with many other proteins, GATA3 also is absent in "triple negative," breast cancers, which are more often fatal. Triple negative breast cancers, which disproportionately affect black women and younger women, do not depend on the hormones, nor do they require a third growth factor, called HER2.

Triple negative breast cancers, which account for roughly one-in-five breast cancers, have been more difficult to target successfully with newer treatments.

"The targeting we would like to do is to give back microRNA29b specifically to breast tumor cells to prevent metastasis," Werb said.

UCSF Co-authors who contributed to the research include medical student Jonathan Chou, PhD, technician Jeffrey Lin, research specialist Audrey Brenot, PhD, and postdoctoral fellows Jung-whan Kim, PhD, and Sylvain Provot, PhD.

The research was funded by the National Institutes of Health and the Department of Defense.

UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care.

Jeffrey Norris | EurekAlert!
Further information:
http://www.ucsf.edu

More articles from Health and Medicine:

nachricht Why might reading make myopic?
18.07.2018 | Universitätsklinikum Tübingen

nachricht Unique brain 'fingerprint' can predict drug effectiveness
11.07.2018 | McGill University

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

Im Focus: Chemical reactions in the light of ultrashort X-ray pulses from free-electron lasers

Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.

Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

Global study of world's beaches shows threat to protected areas

19.07.2018 | Earth Sciences

New creepy, crawly search and rescue robot developed at Ben-Gurion U

19.07.2018 | Power and Electrical Engineering

Metal too 'gummy' to cut? Draw on it with a Sharpie or glue stick, science says

19.07.2018 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>