Constitutive activation of NF-kappaB in primary adult T-cell leukemia cells.
Human T-cell leukemia virus type I (HTLV-I) is an etiologic agent of adult T-cell leukemia (ATL). The viral protein Tax induces the activation and nuclear translocalization of transcription factor NF-kappaB, which is proposed to play a crucial role in the transformation of T cells by HTLV-I. However, the HTLV-I genes including Tax are not expressed significantly in primary leukemic cells from ATL patients. In this study, we examined the basis for NF-kappaB activation in freshly isolated leukemic cells from ATL patients. We found that leukemic cells from ATL patients, like HTLV-I-infected T-cell lines, display constitutive NF-kappaB DNA binding activity and increased degradation of IkappaBalpha (an inhibitor of NF-kappaB). Whereas the NF-kappaB binding activity in Tax-expressing T-cell lines consisted mostly of p50/c-Rel, fresh ATL samples contained p50/p50 and p50/p65 heterodimers. One T-cell line derived from ATL leukemic cells, TL-Om1, displayed constitutive NF-kappaB activity, as well as enhanced degradation of IkappaBalpha, despite the lack of detectable Tax expression. Interestingly, the NF-kappaB in TL-Om1 consists of p50/p50 and p50/p65 like that in fresh primary leukemic cells. Our results suggest that activation of NF-kappaB occurs through a Tax-independent mechanism in leukemic cells of ATL patients, possibly due to differential NF-kappaB subunit activation.
Mori
N
N
Department of Preventive Medicine and AIDS Research, Research Field of Pathogenesis and Clinical Sciences, Institute of Tropical Medicine, Nagasaki University, Japan.
Fujii
M
M
Ikeda
S
S
Yamada
Y
Y
Tomonaga
M
M
Ballard
D W
DW
Yamamoto
N
N
D004273:DNA, Neoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D015973:Gene Expression Regulation, Leukemic; D016356:Gene Products, tax / Q000502:physiology; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000502:physiology; D006801:Humans; D020672:I-kappa B Proteins; D019169:Jurkat Cells / Q000378:metabolism; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics / Q000378:metabolism*; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D052002:NF-kappa B p50 Subunit; D009363:Neoplasm Proteins / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D020569:Proto-Oncogene Proteins c-rel; D011993:Recombinant Fusion Proteins / Q000502:physiology; D013601:T-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D051996:Transcription Factor RelA; D014162:Transfection; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D016356:Gene Products, tax; D020672:I-kappa B Proteins; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; C000606204:NFKBIA protein, human; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D020569:Proto-Oncogene Proteins c-rel; D011993:Recombinant Fusion Proteins; D051996:Transcription Factor RelA; D000072000:NF-KappaB Inhibitor alpha