Characterization of mRNA expression of IkappaB alpha and NF-kappaB subfamilies in primary adult T-cell leukemia cells.
Tax protein of HTLV-1 activates the transcriptional capacity of the NF-kappaB family, resulting in up-regulation of various genes, which are linked to phenotypic alterations of HTLV-1-infected T cells. To understand NF-kappaB regulation in HTLV-1-infected leukemic cells in vivo, we analyzed expression of NF-kappaB and IkappaB alpha in primary cells isolated from ATL patients. Using competitive polymerase chain reaction, we observed an elevated expression of IkappaB alpha mRNA in all four ATL cases tested. In contrast to the elevated mRNA levels, the levels of IkappaB alpha protein were remarkably reduced in some of these cases, suggesting destabilization of IkappaB alpha protein. On the other hand, mRNA expression of p50/p105 and p65, subfamilies of NF-kappaB, was enhanced in primary cells isolated from some ATL patients. Furthermore, the expression patterns of NF-kappaB subfamily were variable among patients and also different from those in T cells isolated from uninfected individuals. Although the number of cases analyzed was limited, we can conclude from these observations that activation of NF-kappaB is restricted to a few subfamilies in vivo. These findings in vivo are strikingly different from those in HTLV-1-infected T cell lines in vitro, in which Tax is responsible for NF-kappaB activation. It is therefore suggested that the elevation of NF-kappaB expression in leukemic cells of ATL patients might not be supported mainly by the viral protein Tax.
Inoue
M
M
Department of Cellular and Molecular Biology, The Institute of Medical Science, The University of Tokyo.
Matsuoka
M
M
Yamaguchi
K
K
Takatsuki
K
K
Yoshida
M
M
D015153:Blotting, Western; D006801:Humans; D019169:Jurkat Cells; D015458:Leukemia, T-Cell / Q000378:metabolism*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051841:Transcription Factor RelB; D014157:Transcription Factors; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; C497593:RELB protein, human; D012333:RNA, Messenger; D014157:Transcription Factors; D051841:Transcription Factor RelB