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

y 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."


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

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