In:
Blood, American Society of Hematology, Vol. 94, No. 9 ( 1999-11-01), p. 3129-3134
Abstract:
The transcription factor NF kappa B (NF-κB) mediates the expression of numerous genes involved in diverse functions such as inflammation, immune response, apoptosis, and cell proliferation. We recently identified constitutive activation of NF-κB (p50/p65) as a common feature of Hodgkin/Reed-Sternberg (HRS) cells preventing these cells from undergoing apoptosis and triggering proliferation. To examine possible alterations in the NF-κB/IκB system, which might be responsible for constitutive NF-κB activity, we have analyzed the inhibitor I kappa B alpha (IκB) in primary and cultured HRS cells on protein, mRNA, and genomic levels. In lymph node biopsy samples from Hodgkin’s disease patients, IκB mRNA proved to be strongly overexpressed in the HRS cells. In 2 cell lines (L428 and KM-H2), we detected mutations in the IκB gene, resulting in C-terminally truncated proteins, which are presumably not able to inhibit NF-κB–DNA binding activity. Furthermore, an analysis of the IκB gene in single HRS cells micromanipulated from frozen tissue sections showed a monoallelic mutation in 1 of 10 patients coding for a comparable C-terminally truncated IκB protein. We suggest that the observed IκB mutations contribute to constitutive NF-κB activity in cultured and primary HRS cells and are therefore involved in the pathogenesis of these Hodgkin’s disease (HD) patients. The demonstrated constitutive overexpression of IκB in HRS cells evidences a deregulation of the NF-κB/IκB system also in the remaining cases, probably due to defects in other members of the IκB family.
Type of Medium:
Online Resource
ISSN:
1528-0020
,
0006-4971
DOI:
10.1182/blood.V94.9.3129
Language:
English
Publisher:
American Society of Hematology
Publication Date:
1999
detail.hit.zdb_id:
1468538-3
detail.hit.zdb_id:
80069-7
