Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Study suggests Akt3 protein is key to melanoma’s resistance to chemotherapy

14.12.2004


Wiping out a protein in skin cancer cells could significantly stall melanoma tumor development and increase the sensitivity of the cancer cells to chemotherapy, a Penn State College of Medicine study suggests.



The protein, Akt3, appears to be responsible for promoting tumor cell survival and development in 43 percent to 60 percent of non-inherited melanomas. "Our study showed that lowering Akt3 activity can reduce the tumor-creating potential of melanoma cells by making the cancer cells more likely to respond to signals that tell them to die," said Gavin P. Robertson, Ph.D., assistant professor of pharmacology, pathology and dermatology, Penn State College of Medicine. "Because most chemotherapeutic drugs work by inducing apoptosis, or programmed cell death, we predict that inhibiting Akt3 activity could lower the threshold doses of drugs or radiation required for effective chemo- or radiotherapy and provide a mechanism to directly target the melanoma cells."

The study, published recently in the journal Cancer Research, used melanoma cell lines together with tumors taken directly from melanoma patients to show that as melanoma cells become more aggressive and metastatic, the amount of active Akt3 protein in the cells increases.


In non-cancerous cells, another protein called PTEN – phosphatase and tensin homologue – starts a chain reaction ensuring that malfunctioning and damaged cells are killed. But abnormal cancerous cells gain the ability to switch off PTEN, allowing dysfunctional, cancerous cells to survive and thrive.

This study exposes another link in that chain reaction by connecting PTEN to Akt3 in melanomas. Robertson found that PTEN specifically regulates Akt3. Consequently, when PTEN is lost, Akt3 malfunctions and accumulates, allowing melanoma cells to survive. "In addition to the connection to PTEN, we also found that more copies of the Akt3 gene are present as melanoma cells become more aggressive," Robertson said. "The Akt3, in effect, protects the cancer cells from the normal signals that would tell them to die. Using samples of human melanoma tumors, we found that levels of active Akt3 increase progressively during melanoma tumor progression with highest levels present in advanced-stage melanoma."

Akt3 is one of a trio of Akt proteins, all three of which have been implicated in various cancers. For example, Akt2 activity has been found in cancers of the ovary, pancreas, stomach and breast. Although all three forms of Akt are present in melanoma cells, this study found that in melanoma, Akt1 and Akt2 remain inactive and, therefore, have little if any role in melanoma development.

Robertson used siRNA, small interfering ribonucleic acids, which can be made to reduce the amount of a specific protein produced by a cell disrupting the synthesis of the protein. In Robertson’s study, the siRNA were designed specifically to target Akt3. In addition, he put back the PTEN protein in the melanoma cells. This restarted the normal signals triggering cell death that had been halted by the melanoma cells. Both of these methods reduced melanoma cell survival and inhibited tumor development. Robertson’s team confirmed this using a mouse model, finding that decreasing Akt3 activity using siRNA or reintroducing the missing PTEN protein halted tumor progression.

"Identifying Akt3 as a possible target to halt the growth of and kill melanoma cells provides new opportunities to develop therapies for patients with metastatic melanoma," Robertson said. "Ultimately, therapies targeted against Akt3 could be used with traditional chemotherapy to give those with melanoma more effective therapeutic options to fight the disease."

This research was supported by the American Cancer Society and The Foreman Foundation for Melanoma Research.

In addition to Robertson, the study team included: Jill M. Stahl, Arati Sharma, Mitchell Cheung, Melissa Zimmerman, Mark Kester, and Lakshman Sandirasegarane, Penn State College of Medicine, Jin Q. Cheng, University of South Florida College of Medicine, and Marcus W. Bosenberg, The University of Vermont.

Valerie Gliem | EurekAlert!
Further information:
http://www.psu.edu

More articles from Studies and Analyses:

nachricht Multi-year study finds 'hotspots' of ammonia over world's major agricultural areas
17.03.2017 | University of Maryland

nachricht Diabetes Drug May Improve Bone Fat-induced Defects of Fracture Healing
17.03.2017 | Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke

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: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Northern oceans pumped CO2 into the atmosphere

27.03.2017 | Earth Sciences

Fingerprint' technique spots frog populations at risk from pollution

27.03.2017 | Life Sciences

Big data approach to predict protein structure

27.03.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>