Die Inhibition von NF-kappaB führt unabhängig vom Amplifikationsstatus des REL-Genes zu einem verlangsamten Wachstum von B-Zell-Lymphom-Zelllinien in vitro.
Amplifications of the NFkB gene REL are a common finding in B-cell lymphomas, but to date, there is not much known about functional consequences of this amplicon. We used 10 B-cell lymphoma cell lines and 23 samples of GI lymphomas to search for the associated biologic features of REL-amplified B-cell lymphomas compared to not-amplified lymphomas. We found REL-amplifications in 6 out of 10 cell lines and 6 out of 23 lymphoma samples and searched for correlations of the genomic REL-copy number with expression, activity, inducibility, dependence on cRel regarding survival and proliferation, with mutations and with variant splicing of REL-mRNA. We did not find any correlation of the genomic copy number of REL compared with any of the attributes mentioned above; we did find a global dependence of lymphoma cell line proliferation on the MALT-1 protease and a dependence of the survival on the IKK, without any influence of the REL-amplicon. Furthermore, we identified a to date not known single-nucleotide mutation of REL and a high molecular wight modification of REL that occured after inhibiting the IKK. Finally, we showed that measuring nuclear cRel-protein is a valid method for measuring cRel-activity in spite of the fact that active cRel is "shuttling" through the nucleus.
Subject HeadingsGenamplifikation [GND]
Nuklearfaktor Kappa B [GND]
Gene amplification [MeSH]
NF-kappa B [MeSH]