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 Immune Defense Without Collateral Damage
23.01.2017 | Universität Basel

nachricht The interactome of infected neural cells reveals new therapeutic targets for Zika
23.01.2017 | D'Or Institute for Research and Education

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Quantum optical sensor for the first time tested in space – with a laser system from Berlin

For the first time ever, a cloud of ultra-cold atoms has been successfully created in space on board of a sounding rocket. The MAIUS mission demonstrates that quantum optical sensors can be operated even in harsh environments like space – a prerequi-site for finding answers to the most challenging questions of fundamental physics and an important innovation driver for everyday applications.

According to Albert Einstein's Equivalence Principle, all bodies are accelerated at the same rate by the Earth's gravity, regardless of their properties. This...

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

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...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | 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

 
Latest News

Tracking movement of immune cells identifies key first steps in inflammatory arthritis

23.01.2017 | Health and Medicine

Electrocatalysis can advance green transition

23.01.2017 | Physics and Astronomy

New technology for mass-production of complex molded composite components

23.01.2017 | Process Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>