Navigation Links
Study identifies key molecules in multiple myeloma
Date:10/26/2010

COLUMBUS, Ohio 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."


'/>"/>

Contact: Darrell E. Ward
Darrell.Ward@osumc.edu
614-293-3737
Ohio State University Medical Center
Source:Eurekalert

Related biology news :

1. Landenberger Foundation awards grant to Scripps Florida scientist to study HIV
2. Penn study identifies molecular guardian of cells RNA
3. LSUHSC study IDs proteins regulating water retention in salt-sensitive hypertension
4. Offshore wind a mixed bag: University of Maryland study
5. Modeling study identifies characteristics of high elk-use areas in western Oregon, Washington
6. Universities receive grants to study climate change decisions
7. Center to study effects of plastics chemicals on childrens health
8. Study of tiny magnets may advance their use in microelectronics
9. BMC receives National Institutes of Health grant to study intrauterine cocaine and substance reslience
10. CRN responds to JAMA fish oil study
11. Singapore scientists first to perform genome-wide study of human stem cells
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:3/14/2016)... , Allemagne, March 14, 2016 ... ) - --> - Renvoi : image ... --> --> ... biométriques, fournit de nouveaux lecteurs d,empreintes digitales pour ... de DERMALOG sera utilisé pour produire des cartes ...
(Date:3/10/2016)... , March 10, 2016 ... market research report "Identity and Access Management Market by ... Compliance, and Governance), by Organization Size, by Deployment, by ... published by MarketsandMarkets, The market is estimated to grow ... Billion by 2020, at a Compound Annual Growth Rate ...
(Date:3/9/2016)... HAMBURG, Germany , March 9, 2016 ... African country,s government identified that more than 23,000 public ... name or had been receiving their salary unlawfully.    ... West African country,s government identified that more than 23,000 ... recorded name or had been receiving their salary unlawfully. ...
Breaking Biology News(10 mins):
(Date:5/25/2016)... (PRWEB) , ... May 25, 2016 , ... ... features a variety of fracture-specific plating options designed to address fractures of the ... fracture fixation solutions. , The Acumed Ankle Plating System 3 is composed of ...
(Date:5/25/2016)... (PRWEB) , ... May 25, 2016 , ... Lady had ... she tore her cruciate ligament in her left knee. Lady’s owner Hannah sought the ... central Florida board-certified veterinary surgeon, to repair her cruciate ligament and help with the ...
(Date:5/24/2016)... ... May 24, 2016 , ... ... identity. The new Media Cybernetics corporate branding reflects a results-driven revitalization for a ... image analysis. The re-branding components include a crisp, refreshed logo and a new ...
(Date:5/23/2016)... and LONDON , May 23, 2016 ... Frontage Boost Efficiency by 40% - Frontage Implement a ... Frontage Enforce Quality, Compliance and Traceability Within the Bioanalytical lab ... in the United States and ... be deployed across its laboratory facilities. In addition to serving as ...
Breaking Biology Technology: