PMID- 18187570
OWN - NLM
STAT- MEDLINE
DCOM- 20080408
LR  - 20181113
IS  - 0002-9440 (Print)
IS  - 1525-2191 (Electronic)
IS  - 0002-9440 (Linking)
VI  - 172
IP  - 2
DP  - 2008 Feb
TI  - CD30-induced signaling is absent in Hodgkin's cells but present in anaplastic 
      large cell lymphoma cells.
PG  - 510-20
LID - 10.2353/ajpath.2008.070858 [doi]
AB  - 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-kappaB (NF-kappaB), 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-kappaB 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-kappaB-mediated survival. These data suggest 
      that CD30-targeted therapy in ALCL should be combined with NF-kappaB inhibitors 
      to induce effective cell killing.
FAU - Hirsch, Burkhard
AU  - Hirsch B
AD  - Charite-University Medicine Berlin, Campus Benjamin Franklin, Institute of 
      Pathology, D-12200 Berlin, Germany. burkhard.hirsch@charite.de
FAU - Hummel, Michael
AU  - Hummel M
FAU - Bentink, Stefan
AU  - Bentink S
FAU - Fouladi, Fariba
AU  - Fouladi F
FAU - Spang, Rainer
AU  - Spang R
FAU - Zollinger, Raphael
AU  - Zollinger R
FAU - Stein, Harald
AU  - Stein H
FAU - Durkop, Horst
AU  - Durkop H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080110
PL  - United States
TA  - Am J Pathol
JT  - The American journal of pathology
JID - 0370502
RN  - 0 (Ki-1 Antigen)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Small Interfering)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Apoptosis/physiology
MH  - Caspases/metabolism
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - Electrophoretic Mobility Shift Assay
MH  - Enzyme Activation/physiology
MH  - Flow Cytometry
MH  - Gene Expression
MH  - Gene Expression Profiling
MH  - *Gene Expression Regulation, Neoplastic
MH  - Hodgkin Disease/*metabolism
MH  - Humans
MH  - Immunoblotting
MH  - Ki-1 Antigen/*metabolism
MH  - Lymphoma, Large-Cell, Anaplastic/*metabolism
MH  - NF-kappa B/metabolism
MH  - Oligonucleotide Array Sequence Analysis
MH  - RNA, Small Interfering
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Signal Transduction/*physiology
MH  - Transfection
PMC - PMC2312360
EDAT- 2008/01/12 09:00
MHDA- 2008/04/09 09:00
PMCR- 2008/08/01
CRDT- 2008/01/12 09:00
PHST- 2008/01/12 09:00 [pubmed]
PHST- 2008/04/09 09:00 [medline]
PHST- 2008/01/12 09:00 [entrez]
PHST- 2008/08/01 00:00 [pmc-release]
AID - S0002-9440(10)61815-9 [pii]
AID - 10.2353/ajpath.2008.070858 [doi]
PST - ppublish
SO  - Am J Pathol. 2008 Feb;172(2):510-20. doi: 10.2353/ajpath.2008.070858. Epub 2008 
      Jan 10.