title: HSP90 is essential for Jak-STAT signaling in classical Hodgkin lymphoma cells.
abstract: In classical Hodgkin lymphoma (cHL) chemotherapeutic regimens are associated with stagnant rates of secondary malignancies requiring the development of new therapeutic strategies. We and others have shown that permanently activated Signal Transducer and Activator of Transcription (STAT) molecules are essential for cHL cells. Recently an overexpression of heat-shock protein 90 (HSP90) in cHL cells has been shown and inhibition of HSP90 seems to affect cHL cell survival. Here we analysed the effects of HSP90 inhibition by geldanamycin derivative 17-AAG or RNA interference (RNAi) on aberrant Jak-STAT signaling in cHL cells. Treatment of cHL cell lines with 17-AAG led to reduced cell proliferation and a complete inhibition of STAT1, -3, -5 and -6 tyrosine phosphorylation probably as a result of reduced protein expression of Janus kinases (Jaks). RNAi-mediated inhibition of HSP90 showed similar effects on Jak-STAT signaling in L428 cHL cells. These results suggest a central role of HSP90 in permanently activated Jak-STAT signaling in cHL cells. Therapeutics targeting HSP90 may be a promising strategy in cHL and other cancer entities associated with deregulated Jak-STAT pathway activation.
authors.affiliation: Department of Hematology and Oncology, Medical Center of the Georg-August-University Göttingen, Göttingen, Germany. nschoof@gwdg.de.
authors.forename: Nils
authors.initials: N
authors.lastname: Schoof
authors.forename: Frederike
authors.initials: F
authors.lastname: von Bonin
authors.forename: Lorenz
authors.initials: L
authors.lastname: Trümper
authors.forename: Dieter
authors.initials: D
authors.lastname: Kube