Characterization of mRNA Expression of IκBα and NF‐κB Subfamilies in Primary Adult T‐cell Leukemia Cells

Abstract

Tax protein of HTLV-1 activates the transcriptional capacity of the NF-κ κ κ κB family, resulting in upregulation of various genes, which are linked to phenotypic alterations of HTLV-1-infected T cells. To understand NF-κ κ κ κB regulation in HTLV-1-infected leukemic cells in vivo, we analyzed expression of NF-κ κ κ κB and Iκ κ κ κBα α α α in primary cells isolated from ATL patients. Using competitive polymerase chain reaction, we observed an elevated expression of Iκ κ κ κBα α α α mRNA in all four ATL cases tested. In contrast to the elevated mRNA levels, the levels of Iκ κ κ κBα α α α protein were remarkably reduced in some of these cases, suggesting destabilization of Iκ κ κ κBα α α α protein. On the other hand, mRNA expression of p50/p105 and p65, subfamilies of NF-κ κ κ κB, was enhanced in primary cells isolated from some ATL patients. Furthermore, the expression patterns of NF-κ κ κ κB 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-κ κ κ κB 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-κ κ κ κB activation. It is therefore suggested that the elevation of NF-κ κ κ κB expression in leukemic cells of ATL patients might not be supported mainly by the viral protein Tax.

Activation of NF-κB by HTLV-I and implications for cell transformation

“…It was reported that the NF-kB species highly expressed in ATL cells were different from those observed in T-cell lines infected in vitro; mRNAs for p52/p100 and c-Rel were abundantly expressed in Taxexpressing T-cell lines, whereas those for p50/p105 and RelA were highly expressed in ATL cells (Arima et al, 1991;Crenon et al, 1993;Li et al, 1993;Lanoix et al, 1994;Inoue et al, 1998). Accordingly, NF-kB DNAbinding activity in Tax-expressing T-cell lines was composed predominantly of c-Rel, p50, and p52 (Lanoix et al, 1994;Xiao et al, 2001a), whereas that in Tax-negative HTLV-I-infected T-cell lines and primary ATL cells contained p50 and RelA (Mori al., 1999).…”

High levels of cytoplasmic HTLV-1 Tax mutant proteins retain a Tax-NF-κB-CBP ternary complex in the cytoplasm

“…The oncogenic potential of Tax is partly ascribed to its activation of NF-kB transcription factors (Yoshida, 1994(Yoshida, , 2001Yamaoka et al, 1996;Inoue et al, 1998;Jeang, 2001;Azran et al, 2004) which regulate numerous cellular genes associated with diverse central biological processes (Pahl, 1999;Jeang, 2001;Yamamoto and Gaynor, 2001;Karin and Lin, 2002;Wang et al, 2002;Kucharczak et al, 2003;Azran et al, 2004). The NF-kB family includes the p50(NF-kB1), p52(NF-kB2), p65(RelA), RelB and c-Rel factors that share a common Rel homology domain (RHD), which is involved in their dimerization, DNA binding and nuclear localization.…”

Association of High Proliferation in Adult T-cell Leukemia Cells With Apoptosis, and Expression of p53 Protein in Acute Type ATL

“…[1][2][3][4][5] ATL is clinically subcategorized into smoldering, chronic, acute, and lymphoma types. 1 It is well known that ATL cells in the peripheral blood have so-called flower-shaped nuclei 1 whereas ATL cells in the lymph nodes and the extranodal tissues exhibit variousshaped (pleomorphic) and various-sized (polymorphic) appearances.…”