Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers Identify Key Enzyme in Melanoma Cell Development

18.06.2010
Virginia Commonwealth University researchers have discovered a mechanism by which an enzyme regulates gene expression and growth in melanoma cells, a finding that could someday lead to more effective drugs to attack cancers and make them more treatable.

Melanoma, the most serious type of skin cancer, is highly resistant to current therapeutic strategies for reasons that are not well understood. New research at VCU suggests that an enzyme discovered in 2003 might be used to target a specific genetic component that helps to regulate gene expression and defends melanoma cells against treatment.

The findings are reported online this week in the Proceedings of the National Academy of Sciences.

“By selectively and specifically targeting molecules for degradation that serve as gatekeepers for cancer growth, progression and resistance to therapy, it may be possible to turn the cancer cells’ defense into an offense that can be used as an effective approach to destroy the tumor,” said Paul B. Fisher, Ph.D., professor and chair of the Department of Human and Molecular Genetics and director of the VCU Institute of Molecular Medicine in the VCU School of Medicine.

Several years ago, Fisher led a team of scientists at Columbia University in identifying an enzyme involved in halting the growth of human malignant melanoma and other cancer cells. The enzyme, called human polynucleotide phosphorylase or hPNPaseold-35, drives cancerous cells to irreversibly lose their growth potential and acquire properties of more normal cells, a process called terminal cell differentiation. The enzyme also is important in cellular senescence, when a cell cannot divide anymore and dies. Additionally, the investigators developed new strategies for promoting cancer cell-specific expression of this enzyme, which reduced tumor growth in animal cancer models.

Fisher, now at VCU, and colleagues report that hPNPaseold-35 selectively targets and degrades a genetic component known as microRNA-221. MicroRNAs are short genetic components that act like a volume control knob to regulate the production of defined proteins in cells.

MicroRNAs regulate the expression of more than a third of human genes. In recent years, they have been recognized as causing over- or under-expression of genes linked to the majority of cancers and other diseases. Researchers are exploring microRNAs’ roles to understand how they could be used as potential targets for therapies.

The work by Fisher’s group indicates that showering the cell with the hPNPaseold-35 enzyme preferentially degrades microRNA-221, a microRNA that is elevated in multiple cancers including melanoma and which regulates gene expression that promotes the cancer cells’ ability to thrive and spread. MicroRNA-221 also endows melanoma and other cancers with the capacity to resist chemotherapy.

“The present study provides the first observation that microRNAs may be regulated by selective degradation, providing an entry point for developing novel approaches for the therapy of melanoma and other cancers, Fisher said.

The VCU study also found that interferon-beta, a treatment for melanoma and other cancers, induces cells to produce the enzyme while also interfering with the ability of microRNA-221 to perform. Fisher said this provides one possible explanation for how interferon-beta suppresses growth of melanoma cells.

The work was supported by grants from the National Institutes of Health and the Samuel Waxman Cancer Research Foundation.

Fisher, who also is the first incumbent of the Thelma Newmeyer Corman Endowed Chair in Cancer Research at the VCU Massey Cancer Center, led the investigative team at the VCU School of Medicine, which included Swadesh K. Das, Ph.D., a postdoctoral fellow; Upneet K. Sokhi, graduate student; Sujit K. Bhutia, Ph.D., postdoctoral fellow; Belal Azab, graduate student; Zhao-zhong Su, Ph.D., associate professor in VCU’s Department of Human and Molecular Genetics; and Devanand Sarkar, MBBS, Ph.D., assistant professor the Department of Human and Molecular Genetics and member of the VCU Institute of Molecular Medicine.

About VCU and the VCU Medical Center
Virginia Commonwealth University is a major, urban public research university with national and international rankings in sponsored research. Located on two downtown campuses in Richmond, VCU enrolls more than 32,000 students in 211 certificate and degree programs in the arts, sciences and humanities. Sixty-nine of the programs are unique in Virginia, many of them crossing the disciplines of VCU’s 13 schools and one college. MCV Hospitals and the health sciences schools of Virginia Commonwealth University compose the VCU Medical Center, one of the nation’s leading academic medical centers. For more, see www.vcu.edu.

Anne Buckley | EurekAlert!
Further information:
http://www.vcu.edu

More articles from Life Sciences:

nachricht Research team creates new possibilities for medicine and materials sciences
22.01.2018 | Humboldt-Universität zu Berlin

nachricht Saarland University bioinformaticians compute gene sequences inherited from each parent
22.01.2018 | Universität des Saarlandes

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Artificial agent designs quantum experiments

On the way to an intelligent laboratory, physicists from Innsbruck and Vienna present an artificial agent that autonomously designs quantum experiments. In initial experiments, the system has independently (re)discovered experimental techniques that are nowadays standard in modern quantum optical laboratories. This shows how machines could play a more creative role in research in the future.

We carry smartphones in our pockets, the streets are dotted with semi-autonomous cars, but in the research laboratory experiments are still being designed by...

Im Focus: Scientists decipher key principle behind reaction of metalloenzymes

So-called pre-distorted states accelerate photochemical reactions too

What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...

Im Focus: The first precise measurement of a single molecule's effective charge

For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.

Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...

Im Focus: Paradigm shift in Paris: Encouraging an holistic view of laser machining

At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.

No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...

Im Focus: Room-temperature multiferroic thin films and their properties

Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.

Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

10th International Symposium: “Advanced Battery Power – Kraftwerk Batterie” Münster, 10-11 April 2018

08.01.2018 | Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

 
Latest News

Thanks for the memory: NIST takes a deep look at memristors

22.01.2018 | Materials Sciences

Radioactivity from oil and gas wastewater persists in Pennsylvania stream sediments

22.01.2018 | Earth Sciences

Saarland University bioinformaticians compute gene sequences inherited from each parent

22.01.2018 | Life Sciences

VideoLinks Wissenschaft & Forschung
Overview of more VideoLinks >>>