Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Penn researchers discover a molecular pathway that leads to recurrence of breast cancer

20.09.2005


Study may help find ways to prevent recurrence


The microscopic appearance of cells in recurrent tumors changes, transforming from a cuboidal, epithelial shape in primary tumors (left) to a spindle, fibroblastic shape in recurrent tumors (right). (Credit: Susan Moody, Denise Perez, and Lewis Chodosh, University of Pennsylvania School of Medicine and Cell Press)



Using a recently developed mouse model of breast cancer, a team from the University of Pennsylvania School of Medicine has shown that Snail, a molecule normally important in embryonic development, can promote breast cancer recurrence. They also found that high Snail expression predicts more rapid tumor recurrence in women who have been treated for breast cancer. These observations suggest that Snail may represent a target for cancer therapy.

Among women, breast cancer is the most common cancer worldwide and is the leading cause of cancer mortality. Of the more than 5 million women currently living with a diagnosis of breast cancer, recurrence represents the most common cause of death from this disease. Remarkably, recurrences can appear up to 20 years following surgery, although most occur within the first two years. "Up to 40 percent of women thought to be cancer free following surgery, radiation, and chemotherapy still have tumor cells in their bodies in a dormant state. As such, approaches to prevent cancer recurrence in these women would be broadly applicable," says senior author Lewis A. Chodosh, MD, PhD, Vice Chair of the Department of Cancer Biology and Director of Cancer Genetics at the Abramson Family Cancer Research Institute at Penn. The researchers published their findings in the September 2005 issue of Cancer Cell.


"To this point there are extraordinarily few targets that have been causally implicated in breast cancer recurrence. Consequently, there are few treatments available to offer women who are at risk for recurrence once they have received standard treatments," says Chodosh.

The Penn team of researchers induced breast cancer in the genetically engineered mice by giving doxycycline to turn on the oncogene HER-2/neu. This oncogene is commonly amplified in human breast cancers and is associated with aggressive disease and poor clinical outcome. The researchers then induced these tumors to regress by turning off the HER2/neu oncogene in fully formed tumors. This mimics important aspects of molecularly targeted therapies and leads to the dramatic regression of tumors to a clinically undetectable state. Nevertheless, residual tumor cells lie in a dormant state and later grow out after a month to a year in the mice.

Using microarrays, Chodosh’s team compared recurrent tumors with the original tumors from which they arose. They found that a variety of genes were turned on in recurrent tumors that were not on in the original tumors, including the transcriptional regulatory protein, Snail, which was induced ten-fold. The Penn team also identified changes in the microscopic appearance of the cells in recurrent tumors, which had transformed from a cuboidal, epithelial shape to a spindle, fibroblastic shape - a change associated with more aggressive tumors in humans.

Snail was first identified in fruit flies and later in mice based on its essential role in embryogenesis during a developmental transition in which normal cells undergo a similar change in shape. "Snail controls a complex set of cellular functions that cancer cells appropriate by turning on this master regulatory gene," explains Chodosh.

To prove a cause-and-effect, the researchers added Snail back to the original tumor cells in mice and showed that Snail increased the rate of recurrence.

But could Snail expression play a similar role in women with breast cancer? When the Penn team delved into public databases of breast cancer tissue data, separating cases into those with high levels of Snail and those with low levels of Snail, they found that women whose original breast cancers expressed high levels of Snail were twice as likely to experience a recurrence within five years following surgery compared to women whose cancers expressed low levels of Snail.

The magnitude of risk associated with high Snail expression is comparable to standard prognostic factors such as estrogen-receptor status, HER-2/Neu amplification, tumor size and grade, and lymph node status and - after correcting for the effects of these factors - Snail expression was shown to predict a woman’s risk of recurrence independent of these factors.

Currently, Chodosh and colleagues are exploring the precise molecular mechanism by which Snail triggers breast cancer recurrence, as well as ways of targeting Snail’s signaling pathways as a possible therapeutic approach to prevent recurrence.

Karen Kreeger | EurekAlert!
Further information:
http://www.uphs.upenn.edu

More articles from Studies and Analyses:

nachricht Obstructing the ‘inner eye’
07.07.2017 | Friedrich-Schiller-Universität Jena

nachricht Drone vs. truck deliveries: Which create less carbon pollution?
31.05.2017 | University of Washington

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

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

Im Focus: Manipulating Electron Spins Without Loss of Information

Physicists have developed a new technique that uses electrical voltages to control the electron spin on a chip. The newly-developed method provides protection from spin decay, meaning that the contained information can be maintained and transmitted over comparatively large distances, as has been demonstrated by a team from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute. The results have been published in Physical Review X.

For several years, researchers have been trying to use the spin of an electron to store and transmit information. The spin of each electron is always coupled...

Im Focus: The proton precisely weighted

What is the mass of a proton? Scientists from Germany and Japan successfully did an important step towards the most exact knowledge of this fundamental constant. By means of precision measurements on a single proton, they could improve the precision by a factor of three and also correct the existing value.

To determine the mass of a single proton still more accurate – a group of physicists led by Klaus Blaum and Sven Sturm of the Max Planck Institute for Nuclear...

Im Focus: On the way to a biological alternative

A bacterial enzyme enables reactions that open up alternatives to key industrial chemical processes

The research team of Prof. Dr. Oliver Einsle at the University of Freiburg's Institute of Biochemistry has long been exploring the functioning of nitrogenase....

Im Focus: The 1 trillion tonne iceberg

Larsen C Ice Shelf rift finally breaks through

A one trillion tonne iceberg - one of the biggest ever recorded -- has calved away from the Larsen C Ice Shelf in Antarctica, after a rift in the ice,...

Im Focus: Laser-cooled ions contribute to better understanding of friction

Physics supports biology: Researchers from PTB have developed a model system to investigate friction phenomena with atomic precision

Friction: what you want from car brakes, otherwise rather a nuisance. In any case, it is useful to know as precisely as possible how friction phenomena arise –...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Closing the Sustainability Circle: Protection of Food with Biobased Materials

21.07.2017 | Event News

»We are bringing Additive Manufacturing to SMEs«

19.07.2017 | Event News

The technology with a feel for feelings

12.07.2017 | Event News

 
Latest News

NASA looks to solar eclipse to help understand Earth's energy system

21.07.2017 | Earth Sciences

Stanford researchers develop a new type of soft, growing robot

21.07.2017 | Power and Electrical Engineering

Vortex photons from electrons in circular motion

21.07.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>