Document Detail

Consequences of heat shock protein 72 (Hsp72) expression and activity on stress-induced apoptosis in CD30+ NPM-ALK+ anaplastic large-cell lymphomas.
MedLine Citation:
PMID:  22289917     Owner:  NLM     Status:  MEDLINE    
Understanding the mechanisms that control stress-induced apoptosis is critical to explain how tumours respond to treatment, as cancer cells frequently escape drug toxicity by regulating stress response through heat shock protein (HSP) expression. The overexpression of Hsp72, in particular, results in increased incidence of cell transformation, and correlates with poor prognosis in a wide range of cancers. We have shown that Hsp72 assists folding of oncogenic NPM-ALK kinase in anaplastic large-cell lymphomas (ALCLs), but its role in the maintenance of the malignant phenotype remains uncertain. Therefore, we assessed Hsp72 expression in ALCLs, investigating more in detail the mechanisms that regulate its status and activity. We found that Hsp72 is unique among the HSPs involved in tumourigenesis to be overexpressed in ALK(+) tumours and cell lines and to be induced by stress. Different from other HSPs, Hsp72 prevents cell injury, Bax activation and death by apoptosis in ALK(+) cells, acting both upstream and downstream of mitochondria. Conversely, Hsp72 is underexpressed in ALK(-) ALCL cells, and it is unable to protect cells from apoptosis under stress. Moreover, when Hsp72 expression is reduced following NPM-ALK inhibition, lymphoma cells undergo apoptosis, demonstrating the importance of Hsp72 in regulating ALCL stress response and drug sensitivity.
P Bonvini; E Zorzi; L Mussolin; M Pillon; C Romualdi; M Peron; E S G d'Amore; L Lamant; A Rosolen
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-01-06
Journal Detail:
Title:  Leukemia     Volume:  26     ISSN:  1476-5551     ISO Abbreviation:  Leukemia     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-06-06     Completed Date:  2012-08-07     Revised Date:  2013-03-04    
Medline Journal Info:
Nlm Unique ID:  8704895     Medline TA:  Leukemia     Country:  England    
Other Details:
Languages:  eng     Pagination:  1375-82     Citation Subset:  IM    
Pediatric Onco-Hematology Clinic, University Hospital Padova, Padova, Italy.
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MeSH Terms
Blotting, Western
Cell Proliferation
Gene Expression Profiling
HSP72 Heat-Shock Proteins / genetics,  metabolism*
Immunoenzyme Techniques
Lymphoma, Large-Cell, Anaplastic / metabolism*,  pathology*
Mitochondria / pathology*
Nuclear Proteins / genetics,  metabolism*
Oligonucleotide Array Sequence Analysis
RNA, Messenger / genetics
Real-Time Polymerase Chain Reaction
Receptor Protein-Tyrosine Kinases / genetics,  metabolism*
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction
Tissue Array Analysis
Tumor Markers, Biological / genetics,  metabolism
Reg. No./Substance:
0/HSP72 Heat-Shock Proteins; 0/Nuclear Proteins; 0/RNA, Messenger; 0/Tumor Markers, Biological; 117896-08-9/nucleophosmin; EC Protein-Tyrosine Kinases; EC lymphoma kinase

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