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 The personality factor: How to foster the sharing of research data
06.09.2017 | ZBW – Leibniz-Informationszentrum Wirtschaft

nachricht Europe’s Demographic Future. Where the Regions Are Heading after a Decade of Crises
10.08.2017 | Berlin-Institut für Bevölkerung und Entwicklung

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: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Rainbow colors reveal cell history: Uncovering β-cell heterogeneity

22.09.2017 | Life Sciences

Penn first in world to treat patient with new radiation technology

22.09.2017 | Medical Engineering

Calculating quietness

22.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>