1. ¹DSMZ (Deutsche Sammlung von Mikroorganismen und Zellkulturen), Department of Human and Animal Cell Cultures, Braunschweig, Germany
2. ²Medical School Hannover, Department of Hematology and Oncology, Hannover, Germany

Correspondence: Dr S Nagel, DSMZ, Department of Human and Animal Cell Cultures, Mascheroder Weg 1b, 38124 Braunschweig, Germany. Fax: +49 531 2616 150; E-mail: sna@dsmz.de

Received 18 January 2005; Accepted 24 January 2005; Published online 17 March 2005.

Abstract

Multiple cytokines are secreted by Hodgkin lymphoma (HL) cells, notably interleukin-6 (IL6), which is believed to play a significant pathobiological role in this and certain other tumors. Previous work on prostate carcinoma cells has shown that IL6 expression is activated therein by the homeodomain protein GBX2, which we found to be absent in HL cells. Instead, we observed expression of a closely related gene, HLXB9, albeit restricted to HL cells coexpressing IL6. Treatment of HL cell lines with antisense-oligonucleotides directed against HLXB9, forced expression of recombinant HLXB9, and analysis of reporter gene constructs containing IL6 promoter sequences all confirmed the potential of HLXB9 to drive expression of IL6. Chromosomal rearrangements of the HLXB9 locus at 7q36 were not detected in HL cells unlike AML subsets expressing HLXB9. However, inhibition of certain signal transduction pathways revealed that the phosphatidylinositol 3 kinase (PI3K) pathway contributes to HLXB9 expression. AKT/phospho-AKT analysis revealed constitutively active PI3K signalling in HL cell lines. Downstream analysis of PI3K revealed that E2F3 may mediate activation of HLXB9. Taken together, our data show that the PI3K signalling pathway in HL cells is constitutively activated and promotes HLXB9 expression, probably via E2F3, thereby enhancing malignant expression of IL6.