Tumor necrosis factor receptor-associated factor 1 gene overexpression in B-cell chronic lymphocytic leukemia: analysis of NF-kappa B/Rel-regulated inhibitors of apoptosis
| Autor: | Lothar Bergmann, Heike Stobbe, Hermann Heimpel, Hartmut Döhner, Roland M. Schmid, Dieter Kirchner, Gerd Munzert |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Adult
TRAF2 Oncogene Proteins v-rel Apoptosis Inhibitor Immunology Apoptosis Protein Serine-Threonine Kinases Inhibitor of apoptosis Biochemistry CD19 Inhibitor of Apoptosis Proteins immune system diseases hemic and lymphatic diseases Humans RNA Messenger Aged Regulation of gene expression Aged 80 and over biology I-Kappa-B Kinase NF-kappa B Proteins Cell Biology Hematology Middle Aged Leukemia Lymphocytic Chronic B-Cell TNF Receptor-Associated Factor 1 XIAP I-kappa B Kinase Neoplasm Proteins Up-Regulation Gene Expression Regulation Neoplastic Autocrine Communication Case-Control Studies Cancer research biology.protein Insect Proteins Tumor necrosis factor alpha |
| Zdroj: | Blood. 100(10) |
| ISSN: | 0006-4971 |
| Popis: | B-cell chronic lymphocytic leukemia (B-CLL) is characterized by a resistance toward apoptosis-inducing agents. Nuclear factor-kappaB (NF-kappaB)/Rel has been shown to regulate the expression of antiapoptotic genes, such as members of the inhibitor of apoptosis protein (IAP) and tumor necrosis factor receptor-associated factor (TRAF) gene families. Expression and regulation of NF-kappaB/Rel-dependent inhibitors of apoptosis have not been collectively studied in B-CLL. We examined expression of known NF-kappaB/Rel-regulated antiapoptotic genes by RNAse protection assay, real-time polymerase chain reaction, and immunoblotting in patients with B-CLL. TRAF1 and to a lesser extent TRAF2 were overexpressed in B-CLL lymphocytes as compared with normal CD19(+) B cells. TRAF1 overexpression did not correlate with markers of disease progression or overall survival. Furthermore, we found high constitutive expression of the IAP genes c-IAP-1, c-IAP-2, and XIAP both in normal and B-CLL lymphocytes. Focusing on the regulation of TRAF1, NF-kappaB/Rel activity in B-CLL nuclear extracts was shown to bind to TRAF1 promoter elements. However, IkappaB kinase (IKK) activity was not increased in CLL lymphocytes as compared with normal CD19(+) B cells. The known IKK inhibitor sulfasalazine did not compromise TRAF1 expression. Thus, although our study revealed a common expression pattern of NF-kappaB/Rel-regulated inhibitors of apoptosis, our findings indicate an IKK-independent regulation of TRAF1 in B-CLL. |
| Databáze: | OpenAIRE |
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