| Hedgehog signaling pathway is activated in diffuse large B-cell lymphoma and contributes to tumor cell survival and proliferation. | |
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MedLine Citation:
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PMID: 20200556 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-03-04 |
Journal Detail:
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Title: Leukemia Volume: 24 ISSN: 1476-5551 ISO Abbreviation: Leukemia Publication Date: 2010 May |
Date Detail:
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Created Date: 2010-05-12 Completed Date: 2010-06-03 Revised Date: 2013-03-04 |
Medline Journal Info:
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Nlm Unique ID: 8704895 Medline TA: Leukemia Country: England |
Other Details:
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Languages: eng Pagination: 1025-36 Citation Subset: IM |
Affiliation:
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Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis Blotting, Western Cell Cycle Cell Proliferation* Cell Survival Gene Expression Regulation, Leukemic* Germinal Center / pathology* Hedgehog Proteins / genetics, metabolism* Humans 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 |
| Chemical | |
Reg. No./Substance:
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0/Hedgehog Proteins; 0/RNA, Messenger; 0/Tumor Markers, Biological |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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