Aurora2/BTAK/STK15 is involved in cell cycle checkpoint and cell survival of aggressive non-Hodgkin's lymphoma.

Non-Hodgkin's lymphoma (NHL) has a wide biological heterogeneity and shows extremely variable responses to therapeutic measures. However, markers that indicate disease activity and determine treatment strategies for this malignancy are little recognized. Using the differential display method, we have identified Aurora2/BTAK/STK15, a centrosome-associated serine/threonine kinase, whose overexpression leads to centrosome amplification, chromosomal instability and transformation of mammalian solid tumours. Northern analysis with mRNA from a single tumour cell suspension of NHL confirmed that Aurora2/BTAK/STK15 was highly expressed in histologically aggressive types. To elucidate the function of Aurora2/BTAK/STK15 in NHL, Aurora2/BTAK/STK15 sense or antisense genes were transfected to B-cell lymphoma cell lines to generate overexpressed or under-regulated tumour cells. Aurora2/BTAK/STK15 antisense transfectant was barely established compared with a sense or vector-only transfectant. Two clones were finally established that exhibited a low proliferation rate and significantly increased G1 arrest compared with vector-only transfectants. Moreover, antisense oligo treatment in vitro showed that restriction of cell growth appeared in proportion to antisense oligo concentration. These results suggest that Aurora2/BTAK/STK15 is an effective candidate to indicate not only disease activity but also tumorigenesis of non-Hodgkin's lymphoma. Retardation of tumour cell growth resulting from the restriction of this gene's functions may be a novel therapeutic approach for non-Hodgkin's lymphoma.

Phenotypic and functional alterations of dendritic cells induced by human herpesvirus 6 infection.

Human herpesvirus 6 (HHV-6) has a tropism for T lymphocytes and monocytes/macrophages, suggesting that HHV-6 infection affects the immunosurveillance system. In the present study, we investigated the HHV-6-induced phenotypic and functional alterations of dendritic cells (DCs), which are professional antigen-presenting cells. HHV-6 infection of monocyte-derived immature DCs appeared to induce the up-regulation of CD80, CD83, CD86, and HLA class I and class II molecules, suggesting that HHV-6 infection induces the maturation of DCs. In addition, the antigen capture capacity of DCs was found to decrease following infection with HHV-6. In contrast to up-regulation of mature-DC-associated surface molecules on HHV-6-infected DCs, their capacity for presentation of alloantigens and exogenous virus antigens to T lymphocytes decreased significantly from that of uninfected DCs. In contrast, there appeared to be no reduction in the capacity for presentation of an HLA class II-binding peptide to the peptide-specific CD4(+) T lymphocytes. These data indicate that HHV-6 infection induces phenotypic alterations and impairs the antigen presentation capacity of DCs. The present data also suggest that the dysfunction of HHV-6-infected DCs is attributable mainly to impairment of the antigen capture and intracellular antigen-processing pathways.