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PMID:16108830

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Citation

Nishikori, M, Ohno, H, Haga, H and Uchiyama, T (2005) Stimulation of CD30 in anaplastic large cell lymphoma leads to production of nuclear factor-kappaB p52, which is associated with hyperphosphorylated Bcl-3. Cancer Sci. 96:487-97

Abstract

Anaplastic large cell lymphoma (ALCL) and Hodgkin lymphoma (HL) express CD30 at high levels, but stimulation of this molecule has been reported to induce contradictory effects. To elucidate the molecular mechanism of CD30-mediated apoptosis of ALCL, we compared the gene expression profiles of t(2;5)(p23;q35)-positive ALCL with those of HL altered by CD30 agonistic stimulation. The results showed that BCL3, the high-level expression of which in ALCL was previously reported, was further upregulated in response to CD30 stimulation, along with several pro-apoptotic genes. Bcl-3 protein was present as an intermediate phospho-form in the resting-state ALCL, becoming hyperphosphorylated (Bcl-3P) upon stimulation. We next found that the stimulation promoted de novo synthesis of the nuclear factor (NF)-kappaB2/p100 precursor as well as processing to p52, and a series of immunoprecipitation and western blotting analyses consistently showed association of Bcl-3P with p52 in CD30-stimulated ALCL. An electrophoretic mobility shift assay revealed the induction of kappaB binding activity of the p52 homodimer, and nuclear colocalization of Bcl-3 and p52 was demonstrated in anaplastic lymphoma kinase-positive ALCL tumor tissues by immunohistochemistry. As Bcl-3 can act as an anti-repressor or transactivator or both, we propose that the (p52)2/Bcl-3P ternary complex, which is specifically induced in CD30-stimulated ALCL, can modulate expression of apoptosis-related genes regulated by NF-kappaB, thereby accounting for CD30-mediated apoptosis of ALCL.

Links

PubMed Online version:10.1111/j.1349-7006.2005.00078.x

Keywords

Antigens, CD30/genetics; Carcinoma/genetics; Carcinoma/pathology; Cell Line, Tumor; Chromosomes, Human, Pair 2; Chromosomes, Human, Pair 5; Humans; Lymphoma, Large B-Cell, Diffuse/genetics; Lymphoma, Large B-Cell, Diffuse/pathology; NF-kappa B/genetics; NF-kappa B p52 Subunit; Phosphorylation; Proto-Oncogene Proteins/metabolism; Transcription Factors; Translocation, Genetic

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:NFKB1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P20749

F

Seeded From UniProt

complete

HUMAN:BCL3

enables

GO:0008134: transcription factor binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q00653

F

Seeded From UniProt

complete

HUMAN:BCL3

enables

GO:0008134: transcription factor binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P19838

F

Seeded From UniProt

complete

HUMAN:TNR8

involved_in

GO:0032760: positive regulation of tumor necrosis factor production

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:TNR8

involved_in

GO:0032759: positive regulation of TRAIL production

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:TNR8

involved_in

GO:0043065: positive regulation of apoptotic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:NFKB2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P20749

F

Seeded From UniProt

complete


See also

References

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