Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Genes against Cancer

13.02.2012
Ovarian Cancer: New Tumour Suppressor Gene Identified

A recent study published in CLINICAL CANCER RESEARCH suggests that the protein hVps37A suppresses tumour growth in ovarian cancer. The work, which was funded by the Austrian Science Fund FWF, shows, for the first time, that this protein is significantly reduced in ovarian cancer cells.

The scientists also found that this reduction affects a cellular signalling pathway that is associated with the membrane receptor EGFR (Epidermal Growth Factor Receptor). The receptor is considered an important biological marker for the course of the disease and therapy, and also serves as a target for modern treatment of different cancer types. In fact, the cells in which hVps37A synthesis was reduced showed resistance to Cetuximab, an approved substance for inhibition of EGFR activity.

The hVps37A gene as such is not unknown to scientists. In the period 2004 to 2007, a systematic genome search as part of a project funded by the Austrian Science Fund FWF determined that, among others, this gene is down-regulated in ovarian cancer. The then head of studies, Prof. Michael Krainer, has now studied the function of this gene further in this particular type of cancer. The published results of this follow-up project show that hVps37A is a hitherto unknown tumour suppressor gene.

RECEPTOR FOR SUCCESS
With reference to the study, Prof. Krainer, Director of the Molecular Genetics Working Group, Department of Oncology, University Clinic for Internal Medicine I, Vienna General Hospital, explains: "Our results, which are based on an unparalleled number of tissue samples from ovarian cancer, clearly confirm a significant reduction of hVps37A activity. At the same time, we found that this reduced activity strongly influences the activity of the membrane receptor EGFR. This is an essential indication of the function of hVps37A - and of the importance of our results for other cancer types, in which EGFR activity causes cancer to develop."

The Epidermal Growth Factor Receptor (EGFR) "transmits" signals from the extracellular domain to within the cell. The binding of signal substances on the cell surface of the receptor causes a chemical modification (phosphorylation) of the receptor structure on the side of the cell lumen. This signal subsequently affects numerous cellular processes significantly, including cell proliferation, and may therefore contribute to the development of cancer.

EFFECTIVE DEGRADATION
In a further key experiment, Prof. Krainer´s team was able to show that the proportions of activated and inactive EGFR in certain ovarian cancer cells were clearly adjusted when hVps37A activity was reduced. According to Prof. Krainer, "this result shows that hVps37A plays a crucial role in degrading the activated form of EGFR. In hVps37A-deficient cells, the activated form of EGFR is no longer degraded and therefore continues to greatly affect subsequent cellular processes - something that hVps37A would inhibit." Indeed, it is commonly known that a protein similar to hVps37A is responsible for disposing of certain "obsolete" proteins in membrane vesicles in yeast cells. Prof. Krainer is of the opinion that the human version of the protein could have a similar role to play.

This theory would explain another result found by Prof. Krainer´s group, namely that cancer cells with reduced hVps37A activity become resistant to Cetuximab, but not to Lapatinib. Cetuximab inhibits EGFR-mediated signal transduction; however, the Cetuximab-EGFR complex must then be degraded in order for the therapy to remain effective. In the case of Lapatinib, which directly inhibits EGFR phosphorylation, this is not necessary.

On the whole, the results from this FWF project offer the first fundamental description of a previously unknown tumour suppressor gene in ovarian cancer cells. Its effect on the EGF receptor also makes the tumour suppressor gene relevant for other types of cancer.

Original Publication: hVps37A Status Affects Prognosis and Cetuximab Sensitivity in Ovarian Cancer. M. Wittinger, P. Vanhara, A. El-Gazzar, B. Savarese-Brenner, D. Pils, M. Anees, T. W. Grunt, M. Sibilia, M. Holcmann, R. Horvat, M. Schemper, R. Zeillinger, C. Schöfer, H. Dolznig, P. Horak and M. Krainer. Clinical Cancer Research 2011;17:7816-7827 DOI:10.1158/1078-0432.CCR-11-0408

Picture and text available from Monday, 13 February 2012, 9 am CET at:
http://www.fwf.ac.at/en/public_relations/press/pv201202-en.html
Scientific Contact:
Prof. Michael Krainer
Medical University of Vienna
Spitalgasse 23
1090 Vienna, Austria
T +43 / (0)664 / 183 76 77
E michael.krainer@meduniwien.ac.at
Austrian Science Fund FWF:
Mag. Stefan Bernhardt
Haus der Forschung
Sensengasse 1
1090 Vienna, Austria
T +43 / (0)1 / 505 67 40 - 8111
E stefan.bernhardt@fwf.ac.at
W http://www.fwf.ac.at
Copy Editing & Distribution:
PR&D - Public Relations for Research & Education Mariannengasse 8
1090 Vienna, Austria
T +43 / (0)1 / 505 70 44
E contact@prd.at
W http://www.prd.at

Margot Pechtigam | PR&D
Further information:
http://www.fwf.ac.at

More articles from Life Sciences:

nachricht Human skin is an important source of ammonia emissions
27.05.2020 | Max-Planck-Institut für Chemie

nachricht Biotechnology: Triggered by light, a novel way to switch on an enzyme
27.05.2020 | Westfälische Wilhelms-Universität Münster

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Biotechnology: Triggered by light, a novel way to switch on an enzyme

In living cells, enzymes drive biochemical metabolic processes enabling reactions to take place efficiently. It is this very ability which allows them to be used as catalysts in biotechnology, for example to create chemical products such as pharmaceutics. Researchers now identified an enzyme that, when illuminated with blue light, becomes catalytically active and initiates a reaction that was previously unknown in enzymatics. The study was published in "Nature Communications".

Enzymes: they are the central drivers for biochemical metabolic processes in every living cell, enabling reactions to take place efficiently. It is this very...

Im Focus: New double-contrast technique picks up small tumors on MRI

Early detection of tumors is extremely important in treating cancer. A new technique developed by researchers at the University of California, Davis offers a significant advance in using magnetic resonance imaging to pick out even very small tumors from normal tissue. The work is published May 25 in the journal Nature Nanotechnology.

researchers at the University of California, Davis offers a significant advance in using magnetic resonance imaging to pick out even very small tumors from...

Im Focus: I-call - When microimplants communicate with each other / Innovation driver digitization - "Smart Health“

Microelectronics as a key technology enables numerous innovations in the field of intelligent medical technology. The Fraunhofer Institute for Biomedical Engineering IBMT coordinates the BMBF cooperative project "I-call" realizing the first electronic system for ultrasound-based, safe and interference-resistant data transmission between implants in the human body.

When microelectronic systems are used for medical applications, they have to meet high requirements in terms of biocompatibility, reliability, energy...

Im Focus: When predictions of theoretical chemists become reality

Thomas Heine, Professor of Theoretical Chemistry at TU Dresden, together with his team, first predicted a topological 2D polymer in 2019. Only one year later, an international team led by Italian researchers was able to synthesize these materials and experimentally prove their topological properties. For the renowned journal Nature Materials, this was the occasion to invite Thomas Heine to a News and Views article, which was published this week. Under the title "Making 2D Topological Polymers a reality" Prof. Heine describes how his theory became a reality.

Ultrathin materials are extremely interesting as building blocks for next generation nano electronic devices, as it is much easier to make circuits and other...

Im Focus: Rolling into the deep

Scientists took a leukocyte as the blueprint and developed a microrobot that has the size, shape and moving capabilities of a white blood cell. Simulating a blood vessel in a laboratory setting, they succeeded in magnetically navigating the ball-shaped microroller through this dynamic and dense environment. The drug-delivery vehicle withstood the simulated blood flow, pushing the developments in targeted drug delivery a step further: inside the body, there is no better access route to all tissues and organs than the circulatory system. A robot that could actually travel through this finely woven web would revolutionize the minimally-invasive treatment of illnesses.

A team of scientists from the Max Planck Institute for Intelligent Systems (MPI-IS) in Stuttgart invented a tiny microrobot that resembles a white blood cell...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Dresden Nexus Conference 2020: Same Time, Virtual Format, Registration Opened

19.05.2020 | Event News

Aachen Machine Tool Colloquium AWK'21 will take place on June 10 and 11, 2021

07.04.2020 | Event News

International Coral Reef Symposium in Bremen Postponed by a Year

06.04.2020 | Event News

 
Latest News

German-British Research project for even more climate protection in the rail industry

28.05.2020 | Transportation and Logistics

A special elemental magic

28.05.2020 | Physics and Astronomy

Skoltech scientists get a sneak peek of a key process in battery 'life'

28.05.2020 | Power and Electrical Engineering

VideoLinks
Science & Research
Overview of more VideoLinks >>>