Document Detail

Hedgehog signaling pathway is activated in diffuse large B-cell lymphoma and contributes to tumor cell survival and proliferation.
MedLine Citation:
PMID:  20200556     Owner:  NLM     Status:  MEDLINE    
Hedgehog (HH) signaling is important in the pathogenesis of several malignancies. Recently, we described that HH signaling proteins are commonly expressed in diffuse large B-cell lymphoma (DLBCL); however, the functional role of HH pathway in DLBCL has not been explored. Here, we assessed the possibility that HH pathway activation contributes to the survival of DLBCL. We found that HH signaling inhibition induces predominantly cell-cycle arrest in DLBCL cells of germinal center (GC) B-cell type, and apoptosis in DLBCL cells of activated B-cell (ABC) type. Apoptosis after HH signaling inhibition in DLBCL cells of ABC type was associated with downregulation of BCL2; however HH inhibition was not associated with BCL2 downregulation in DLBCL of GC type. Functional inhibition of BCL2 significantly increased apoptosis induced by HH inhibition in DLBCL cells of both types. We also showed that DLBCL cells synthesize, secrete and respond to endogenous HH ligands, providing support for the existence of an autocrine HH signaling loop. Our findings provide novel evidence that dysregulation of HH pathway is involved in the biology of DLBCL and have significant therapeutic implications as they identify HH signaling as a potential therapeutic target in DLBCL, in particular for those lymphomas expressing the HH receptor smoothened.
R R Singh; J E Kim; Y Davuluri; E Drakos; J H Cho-Vega; H M Amin; F Vega
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-03-04
Journal Detail:
Title:  Leukemia     Volume:  24     ISSN:  1476-5551     ISO Abbreviation:  Leukemia     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-05-12     Completed Date:  2010-06-03     Revised Date:  2013-03-04    
Medline Journal Info:
Nlm Unique ID:  8704895     Medline TA:  Leukemia     Country:  England    
Other Details:
Languages:  eng     Pagination:  1025-36     Citation Subset:  IM    
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
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MeSH Terms
Blotting, Western
Cell Cycle
Cell Proliferation*
Cell Survival
Gene Expression Regulation, Leukemic*
Germinal Center / pathology*
Hedgehog Proteins / genetics,  metabolism*
Lymphoma, Large B-Cell, Diffuse / genetics,  metabolism*,  pathology*
RNA, Messenger / genetics,  metabolism
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction*
Tumor Cells, Cultured
Tumor Markers, Biological / genetics,  metabolism
Reg. No./Substance:
0/Hedgehog Proteins; 0/RNA, Messenger; 0/Tumor Markers, Biological

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