6533b7d8fe1ef96bd126a2da
RESEARCH PRODUCT
HSPH1 inhibition downregulates Bcl-6 and c-Myc and hampers the growth of human aggressive B-cell non-Hodgkin lymphoma
Giusi RuggieroAntonello CabrasSerenella M. PupaMonica TortoretoClaudio TripodoAlessandro M. GianniCarla GuarnottaCristina TringaliMassimo Di NicolaBruno VenerandoFilippo De BraudAlessandra CavanèRoberta ZappasodiNadia ZaffaroniLorenzo Castagnolisubject
Lymphoma B-CellXenograft Model Antitumor AssayDNA-Binding ProteinImmunologyDown-RegulationMice SCIDSettore MED/08 - Anatomia PatologicaBiologyBiochemistryHSP110 Heat-Shock ProteinProto-Oncogene Proteins c-mycMiceDownregulation and upregulationimmune system diseasesCell Line Tumorhemic and lymphatic diseasesHeat shock proteinGene Knockdown TechniquesmedicineAnimalsHumansGene silencingHSP110 Heat-Shock ProteinsAnimals; Cell Line Tumor; DNA-Binding Proteins; Down-Regulation; Gene Knockdown Techniques; HSP110 Heat-Shock Proteins; Humans; Lymphoma B-Cell; Mice; Mice SCID; Proto-Oncogene Proteins c-myc; Xenograft Model Antitumor Assays; Biochemistry; Immunology; Medicine (all); Hematology; Cell BiologyAnimalMedicine (all)Cell BiologyHematologymedicine.diseaseXenograft Model Antitumor AssaysIn vitroLymphomaDNA-Binding ProteinsCell cultureGene Knockdown TechniquesGene Knockdown TechniqueImmunologyProto-Oncogene Proteins c-bcl-6Cancer researchB-Cell Non-Hodgkin LymphomaHumandescription
We have shown that human B-cell non-Hodgkin lymphomas (B-NHLs) express heat shock protein (HSP)H1/105 in function of their aggressiveness. Here, we now clarify its role as a functional B-NHL target by testing the hypothesis that it promotes the stabilization of key lymphoma oncoproteins. HSPH1 silencing in 4 models of aggressive B-NHLs was paralleled by Bcl-6 and c-Myc downregulation. In vitro and in vivo analysis of HSPH1-silenced Namalwa cells showed that this effect was associated with a significant growth delay and the loss of tumorigenicity when 10(4) cells were injected into mice. Interestingly, we found that HSPH1 physically interacts with c-Myc and Bcl-6 in both Namalwa cells and primary aggressive B-NHLs. Accordingly, expression of HSPH1 and either c-Myc or Bcl-6 positively correlated in these diseases. Our study indicates that HSPH1 concurrently favors the expression of 2 key lymphoma oncoproteins, thus confirming its candidacy as a valuable therapeutic target of aggressive B-NHLs.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2015-01-01 | Blood |