Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Study Identifies Key Molecules In Multiple Myeloma

27.10.2010
New research links three molecules to a critical tumor suppressor gene that is often turned off in multiple myeloma, a presently incurable cancer of the blood.

The findings might offer a new strategy for treating this disease and other blood cancers, according to researchers at The Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James) who led the study.

The silenced molecules are called miR-192, miR-194 and miR-215. All of them are microRNAs, a large class of molecules that are master regulators of many important cell processes.

The study, published in the Oct. 19 issue of Cancer Cell, suggests that re-activating these three molecules triggers expression of the P53 tumor suppressor gene. This, in turn, slows the growth and leads to the death of myeloma cells and could provide a new strategy for treating the disease.

“These findings provide a rationale for the further exploration of these microRNAs as a treatment for multiple myeloma, which has few therapeutic options,” says principal investigator Dr. Carlo Croce, professor and chair of Molecular Virology, Immunology and Medical Genetics, and director of the Human Cancer Genetics program at the OSUCCC – James.

Multiple myeloma is a disorder of white blood cells called plasma cells. More than 20,100 Americans are expected to develop the disease this year and some 10,600 are expected to die from it. Myeloma begins as a benign condition called monoclonal gammopathy of undetermined significance (MGUS). Individuals with MGUS can live for many years without treatment. Then, for unknown reasons, this benign condition can evolve into multiple myeloma.

Studies investigating the molecular causes of the disease have shown a relationship between P53 and another gene called MDM2. They have also shown that myeloma cells often have healthy (i.e., unmutated) P53 genes but very little P53 protein. P53 protein levels are restored, however, when MDM2 expression is blocked.

The study by Croce and his collaborators, which examines the role of microRNA in regulating the P53 pathway in myeloma cells, shows the following:

Expression of miR-192, miR-194 and miR-215 in multiple myeloma cells slows their growth and causes their death by activating the P53 gene;

Multiple myeloma cells from patients show high MDM2 expression compared with MGUS cells and normal plasma cells;

Expression of the three microRNAs dramatically lowers MDM2 expression levels and significantly increases P53 levels;

Treating myeloma cells with the three microRNAs plus an MDM2 inhibitor caused a two-fold rise in P53 expression and a three-fold drop in MDM2 expression;

Treating a myeloma mouse model with the three microRNAs caused a 50 percent reduction in tumor size compared with controls; treating the mice with the microRNAs plus an MDM2 inhibitor brought a five-fold reduction in tumor size.

Expression of the three microRNAs reduced the ability of myeloma cells to migrate and metastasize.

Overall, Croce says, “our results provide the basis for developing a microRNA-based therapy for multiple myeloma.”

Funding from the Kimmel Foundation helped support this research.

Other researchers involved in this study were Flavia Pichiorri, Sung-Suk Suh, Cristian Taccioli, Ramasamy Santhanam, Wenchao Zhou, Don M. Benson, Jr., Craig Hofmainster, Hansjuerg Alder, Michela Garofalo, Gianpiero Di Leva, Stefano Volinia, Huey-Jen Lin, Danilo Perrotti and Rami I. Aqeilan from Ohio State University; Alberto Rocci, University of Turin, Turin, Italy; Luciana De Luca, Referral Cancer Center of Basilicata-Crob, Rionero in Vulture, Italy; Michael Kuehl, Center for Cancer Research, National Cancer Institute, USA; and Antonio Palumbo, University of Turin, Turin, Italy.

The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute is one of only 40 Comprehensive Cancer Centers in the United States designated by the National Cancer Institute. Ranked by U.S. News & World Report among the top cancer hospitals in the nation, The James is the 180-bed adult patient-care component of the cancer program at The Ohio State University. The OSUCCC-James is one of only seven funded programs in the country approved by the NCI to conduct both Phase I and Phase II clinical trials.

Related Links:
A high quality JPEG of Carlo M. Croce, MD, is available here.
Darrell E. Ward
Medical Center Communications
614-293-3737
Darrell.Ward@osumc.edu

Darrell E. Ward | EurekAlert!
Further information:
http://www.osumc.edu

More articles from Life Sciences:

nachricht Decoding the genome's cryptic language
27.02.2017 | University of California - San Diego

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

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Safe glide at total engine failure with ELA-inside

On January 15, 2009, Chesley B. Sullenberger was celebrated world-wide: after the two engines had failed due to bird strike, he and his flight crew succeeded after a glide flight with an Airbus A320 in ditching on the Hudson River. All 155 people on board were saved.

On January 15, 2009, Chesley B. Sullenberger was celebrated world-wide: after the two engines had failed due to bird strike, he and his flight crew succeeded...

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...

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

New pop-up strategy inspired by cuts, not folds

27.02.2017 | Materials Sciences

Sandia uses confined nanoparticles to improve hydrogen storage materials performance

27.02.2017 | Interdisciplinary Research

Decoding the genome's cryptic language

27.02.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>