Inhibition of Signal Transducer and Activator of Transcription 6 Activity in the Hodgkin Lymphoma Cell Line L1236 Induces Growth Inhibition and Apoptosis.

Signal transducer and activator of transcription 6 (STAT6) plays a central role in interleukin (IL)-4 and -13 signaling. Upon binding of the cognate receptors by these cytokines, STAT6 becomes phosphorylated by Jak family kinases and subsequently translocates to the nucleus where transcription of its target genes is regulated. Expression of IL-13 and its receptor are common features of Hodgkin lymphoma (HL) tumor cells, the so-called Hodgkin Reed-Sternberg (H-RS) cells, in which this cytokine has been shown to act as an autocrine growth factor. Consequently, constitutively phosphorylated STAT6 with a nuclear localization is a common and distinctive feature of H-RS cells in classical HL. We knocked down STAT6 expression in the HL cell line L1236 with small interfering RNA (siRNA) and found that inhibition of STAT6 activity results in cell growth inhibition, decreased viability and increased apoptosis. The results depict a central role of STAT6 in the growth of H-RS cells and indicate that STAT6 could be a potential target for therapeutic intervention in HL. Moreover, in order to identify the target genes of this transcription factor in H-RS cells, a combined approach of RNA interference and microarray is performed and the results will be presented.