| IRF4 silencing inhibits Hodgkin lymphoma cell proliferation, survival and CCL5 secretion. | |
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MedLine Citation:
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PMID: 21114485 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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Interferon regulatory factor 4 (IRF4) expression is detected in many lymphoid and myeloid malignancies, and may be a promising therapeutic target. IRF4 is strongly expressed in classical Hodgkin lymphoma (cHL) and its expression is up-regulated by CD40L and down-regulated by both anti-proliferative and pro-apoptotic stimuli. This study analysed the effects of IRF4 silencing in a panel of HL-derived cell lines. We demonstrated that IRF4 down-modulation determined a remarkable decrease of both cell number and clonogenic growth in L-1236, L-428, KM-H2 and HDLM-2 cells, but not in IRF4-negative L-540 cells. IRF4 silencing induced apoptosis, as evaluated by caspase-3 activation and Annexin-V staining and up-regulation of the pro-apoptotic molecule Bax. CD40 engagement by both soluble and membrane bound-CD40L almost totally reduced IRF4 down-modulation and growth inhibition by IRF4 silencing in both L-1236 and L-428 cells. Finally, IRF4 silencing decreased CCL5 secretion in all HL cell lines tested and CCL17 in KM-H2 cells. Taken together, our results demonstrated that IRF4 down-modulation by IRF4 silencing was reversed by CD40 engagement, inhibited HL cells proliferation, induced apoptosis and decreased CCL5 secretion, thus suggesting that IRF4 may be involved in HL pathobiology. |
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Authors:
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Donatella Aldinucci; Marta Celegato; Cinzia Borghese; Alfonso Colombatti; Antonino Carbone |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-11-28 |
Journal Detail:
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Title: British journal of haematology Volume: 152 ISSN: 1365-2141 ISO Abbreviation: Br. J. Haematol. Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2010-12-23 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0372544 Medline TA: Br J Haematol Country: England |
Other Details:
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Languages: eng Pagination: 182-90 Citation Subset: IM |
Copyright Information:
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© 2010 Blackwell Publishing Ltd. |
Affiliation:
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Centro di Riferimento Oncologico, IRCCS-National Cancer Institute, Aviano, Italy. daldinucci@cro.it |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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