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 New risk factors for anxiety disorders
24.02.2017 | Julius-Maximilians-Universität Würzburg

nachricht Stingless bees have their nests protected by soldiers
24.02.2017 | Johannes Gutenberg-Universität Mainz

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Stingless bees have their nests protected by soldiers

24.02.2017 | Life Sciences

New risk factors for anxiety disorders

24.02.2017 | Life Sciences

MWC 2017: 5G Capital Berlin

24.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>