CD30-induced up-regulation of the inhibitor of apoptosis genes cIAP1 and cIAP2 in anaplastic large cell lymphoma cells.
OBJECTIVE
Expression of the cytokine receptor CD30 is a typical feature of anaplastic large cell lymphomas (ALCL). CD30-induced effects have a great impact on cell activation and viability.


METHODS
Using Karpas 299 cells, we performed differential display reverse transcriptase polymerase chain reaction (DDRT-PCR) to identify novel genes involved in CD30 signaling in ALCL. Activation of CD30 was induced by treatment with immobilized anti-CD30 antibody. RNA and protein expression were confirmed in different cell lines by Northern and Western blot analysis. Fluorescence-activated cell sorting (FACS) analysis was applied to examine cell viability. Nuclear factor kappaB (NFkappaB) pathways were blocked using a specific inhibitor.


RESULTS
We found strongly enhanced expression of the cellular inhibitor of apoptosis cIAP1 and cIAP2 in Karpas 299 cells stimulated with anti-CD30. Furthermore, we showed that CD30-regulated expression of cIAP1 and cIAP2 was mediated by NFkappaB. Induction of NFkappaB, cIAP1, and cIAP2 correlated with partial protection from apoptotic cell death caused by etoposide. Correspondingly, inhibition of the NFkappaB pathway not only prevented the prevalent antiapoptotic effects mediated by CD30, but even led to CD30-induced apoptosis. Finally, we found enhanced expression of cIAP1 and cIAP2 in several other ALCL cell lines and the HD-derived cell line HDLM-2 upon CD30 stimulation.


CONCLUSIONS
Our results indicate that CD30-mediated protection from apoptosis is a common feature of CD30(+) cells. Therefore, CD30-induced signaling may have a significant impact on the clinical outcome of patients with ALCL.
Hübinger
Gabriele
G
Department of Internal Medicine III, University of Ulm, Ulm, Germany.
Schneider
Christof
C
Stöhr
Dagmar
D
Ruff
Heike
H
Kirchner
Dieter
D
Schwänen
Carsten
C
Schmid
Mathias
M
Bergmann
Lothar
L
Müller
Elke
E
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D045744:Cell Line, Tumor; D005047:Etoposide / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D017730:Ki-1 Antigen / Q000502:physiology*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D016328:NF-kappa B / Q000502:physiology*; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D044767:Ubiquitin-Protein Ligases
D000972:Antineoplastic Agents, Phytogenic; D051034:Inhibitor of Apoptosis Proteins; D017730:Ki-1 Antigen; D016328:NF-kappa B; D009363:Neoplasm Proteins; D011506:Proteins; D005047:Etoposide; C494833:BIRC2 protein, human; D044767:Ubiquitin-Protein Ligases