Hirsch, Burkhard and Hummel, Michael and Bentink, Stefan and Fouladi, Fariba and Spang, Rainer and Zollinger, Raphael and Stein, Harald and Duerkop, Horst (2008) CD30-induced signaling is absent in Hodgkin's cells but present in anaplastic large cell lymphoma cells. AMERICAN JOURNAL OF PATHOLOGY, 172 (2). pp. 510-520. ISSN 0002-9440,
Full text not available from this repository. (Request a copy)Abstract
High CD30 expression in classical Hodgkin's lymphoma and anaplastic large cell lymphoma. (ALCL) suggests an important pathogenic role of this cytokine receptor. To test this hypothesis, we investigated CD30 signaling in Hodgkin's and ALCL cell lines by different approaches: 1) CD30 stimulation, 2) CD30 down-regulation, and 3) a combination of both. The effects were determined at the RNA (microarray and real-time quantitative RT-PCR), protein (electrophoretic mobility shift analysis, immunoblot, and flow cytometry), and cellular/functional (proliferation and apoptosis) levels. We demonstrate that Hodgkin's cells are virtually CD30 unresponsive. Neither CD30 stimulation nor CD30 silencing of Hodgkin's cells had any significant effect. In contrast, CD30 stimulation of ALCL cells activated nuclear transcription factor-kappa B (NF-kappa B), induced major transcriptional changes, and decreased proliferation. These effects could be abrogated by down-regulation of CD30. Stimulation of CD30 in ALCL cells, stably transfected with a dominant-negative NF-kappa B inhibitor, induced pronounced caspase activation and massive apoptosis. Our data indicate that 1) CD30 signaling is not effective in Hodgkin's cell lines but is effective in ALCL cell lines, 2) CD30 is probably not significantly involved in the pathogenesis of classical Hodgkin's lymphoma, and 3) CD30 stimulation triggers two competing effects in ALCL cells, namely activation of caspases and NF-kappa B-mediated survival. These data suggest that CD30-targeted therapy in ALCL should be combined with NF-kappa B inhibitors to induce effective.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NF-KAPPA-B; REED-STERNBERG CELLS; INDUCED APOPTOSIS; CYCLE ARREST; CD30 LIGAND; ACTIVATION; EXPRESSION; PATHWAYS; DISEASE; GENES; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Institut für Funktionelle Genomik > Lehrstuhl für Statistische Bioinformatik (Prof. Spang) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 09 Nov 2020 12:33 |
| Last Modified: | 09 Nov 2020 12:33 |
| URI: | https://pred.uni-regensburg.de/id/eprint/31386 |
Actions (login required)
 |
View Item |
