Targeted Repression of Overexpressed CD30 Downregulates NF-κB and ERK1/2 Pathway in Hodgkin Lymphoma Cell Lines
Abstract:We previously reported that CD30 is induced during lymphocyte transformation and that overexpressed CD30 can transduce ligand-independent signals in Hodgkin lymphoma (HL) cells. However, its biological consequence is not fully addressed. In this study, we examined the effects of targeted repression of overexpressed CD30 on cell signaling and proliferation using small-interfering RNAs (siRNAs) in HL cell lines. Repression of CD30 inhibited cellular proliferation through reduced activation of IκB kinase (IKK) and extracellular signal-regulated kinase (ERK) 1/2 in both B- and T-HL cell lines. These HL cell lines bear one or more defects in negative regulators of nuclear factor (NF)-κB signaling, including A20, cylindromatosis tumor suppressor protein (CYLD), and IκBα, and when CD30 is repressed, they show reduced activation of the canonical NF-κB pathway. This suggests that CD30 governs NF-κB and ERK1/2 signaling pathways, and is involved in the proliferation of HL cells. Defective mutations in negative regulators of NF-κB signaling appear to promote CD30-initiated basal NF-κB activation. These results indicate that CD30 is involved in the tumorigenic process of HL, and that it may be useful as a therapeutic target for the treatment of HL.
Document Type: Research Article
Publication date: October 1, 2012
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