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 Rainbow colors reveal cell history: Uncovering β-cell heterogeneity
22.09.2017 | DFG-Forschungszentrum für Regenerative Therapien TU Dresden

nachricht The pyrenoid is a carbon-fixing liquid droplet
22.09.2017 | Max-Planck-Institut für Biochemie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Rainbow colors reveal cell history: Uncovering β-cell heterogeneity

22.09.2017 | Life Sciences

Penn first in world to treat patient with new radiation technology

22.09.2017 | Medical Engineering

Calculating quietness

22.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>