Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Switch of a gene turns cancer cells healthy in mice

11.10.2004


Conventional wisdom holds that cancer cells contain so many mutations that there’s no way to return them to the straight and narrow path of their normal neighbors. This has led to cancer treatments that focus on destroying or removing the cancerous cells.



But new research by Dean Felsher, MD, PhD, assistant professor of medicine (oncology) and of pathology at the Stanford University School of Medicine, suggests that cancer cells can be reformed. His work, published in the Oct. 10 advance online issue of Nature, could lead to new ways of treating the most common forms of cancer. Felsher found that turning off just one cancer-causing gene is enough to eliminate aggressive, incurable liver tumors in mice in just four weeks. These cells still had the mutations that made them cancerous in the first place, except that one. He had documented a similar phenomenon in bone cancer two years ago, but liver cancer is more common and difficult to cure. "This is a terrible cancer," said Felsher. "Anything that is encouraging in liver cancer may be important."

Liver cancer is formed in a type of cells called epithelial cells - the same ones that form cancers in the breast, colon and prostate. Felsher’s findings about liver cancer could also apply to these types of cancer. Felsher hopes his work pushes people to find drugs that specifically hamstring the protein in question: Myc (pronounced "mick"), which is one of the most commonly mutated oncogenes in cancer cells.


Myc protein acts as a cellular conductor, orchestrating messages that tell a cell to divide. Normal cells only make the protein when it’s time to multiply. Cancer cells produce too much of this protein all the time, constantly prodding themselves to divide.

In his work, Felsher studied mice whose liver cells he had altered to carry a modified Myc gene. Unlike the normal gene, this one is constantly on. This means that it churned out the Myc protein - until Felsher turned it off. And turning it off is as simple as feeding mice the antibiotic doxycycline.

The mice remained cancer-free as long as they maintained their diet of the antibiotic. But as soon as Felsher withheld the doxycycline, the gene was back on; Myc protein accumulated in the liver cells, and the animals developed aggressive liver cancer within an average of 12 weeks.

Returning these cancer-laden mice to the doxycycline diet again turned off the production of Myc protein and eliminated the cancer. After doing that, Felsher saw normal-appearing liver cells - a finding that was confirmed by his collaborators, Boris Ruebner, Alexanxer Borowski and Robert Cardiff at University of California-Davis.

Together, the researchers found that turning the Myc gene on and off acted like a tap, releasing the cancerous cells to divide uncontrollably then shutting off their cancerous progression. "The exciting thing is that you can turn cancer cells into something that appears to be normal," Felsher said.

Still, some of these those normal-looking cells were simply dormant and retained the ability to become cancerous. This finding could explain why cancers recur after chemotherapy. If the treatment only turns the cancer cells dormant, they can easily become cancerous again at a later time.

One concern Felsher and his colleagues had is whether the liver cells were truly going in and out of a cancerous state, or if new cancers formed each time they reactivated the Myc gene. To settle this question they needed a way to watch the cancerous cells to see whether they regressed to a normal state or died when Myc was turned off.

The solution came through a collaboration with Christopher Contag, PhD, assistant professor of pediatrics, radiology and microbiology and immunology at the Stanford medical school. Felsher and his group created liver tumor cells containing a green cellular beacon that can be detected by a super-sensitive camera developed by Contag and his colleagues. When these marked cells were injected into mice, they quickly formed liver cancers. Feeding the mice doxycyclin again turned off Myc and eliminated the cancer.

But this time around, the researchers could easily detect the cells because of their green label. Aside from their color, they looked like normal liver cells and produced liver proteins. These cells were proof that turning off the Myc gene alters the cell’s fate rather than killing it outright.

The hurdle now is finding drugs that deactivate the Myc gene in humans. Felsher’s experiments worked because the group could create a modified Myc gene that responds to doxycycline. To work that same trick in human cancers, researchers need a drug that binds to the Myc protein and renders it useless.

Amy Adams | EurekAlert!
Further information:
http://www.stanford.edu

More articles from Life Sciences:

nachricht How gut bacteria can make us ill
18.01.2017 | Helmholtz-Zentrum für Infektionsforschung

nachricht Nanoparticle Exposure Can Awaken Dormant Viruses in the Lungs
16.01.2017 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

Im Focus: How to inflate a hardened concrete shell with a weight of 80 t

At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).

Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

Nothing will happen without batteries making it happen!

05.01.2017 | Event News

 
Latest News

How gut bacteria can make us ill

18.01.2017 | Life Sciences

On track to heal leukaemia

18.01.2017 | Health and Medicine

Water - as the underlying driver of the Earth’s carbon cycle

17.01.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>