Growth inhibition of Tax-activated human Jurkat leukemia T cells by all-trans retinoic acid requires JNK-1 inhibition

Parra,Eduardo; Gutiérrez,Luis

doi:10.3892/or.2012.2108

Growth inhibition of Tax-activated human Jurkat leukemia T cells by all-trans retinoic acid requires JNK-1 inhibition

Authors:
- Eduardo Parra
- Luis Gutiérrez
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Affiliations: Biomedical Experimental Laboratory, Faculty of Sciences, University of Tarapaca, Arica, Chile, Faculty of Sciences, Arturo Prat University, Iquique, Chile
Published online on: October 26, 2012 https://doi.org/10.3892/or.2012.2108
Pages: 387-393

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Abstract

Retinoids, including vitamin A (retinol) and its analogues, are critical for a variety of biological functions. In this study, we report that all-trans retinoic acid (ATRA) decreases Jun N-terminal kinase 1 (JNK-1) activity, antagonizing the effect of the Tax protein in Jurkat leukemia T cells transiently transfected for expressing the Tax protein. The Tax protein is one of the products of the human T-cell leukemia virus type 1 (HTLV-1) which is the etiologic agent of adult T-cell leukemia (ATL), an aggressive neoplasia of CD4+ T cells. The decrease in JNK-1 activity was followed by a marked decrease in the expression of interleukin (IL)-2 and a weak increase in interferon (IFN)-γ in Jurkat cells treated with ATRA in a dose-dependent manner, suggesting a correlation between the expression of JNK-1 and the activity of the Tax protein. However, the expression levels of IL-4 and IL-10 were enhanced in cells transfected with Tax, compared with the levels in untransfected cells, but the expression levels were not affected following ATRA treatment. In transfection studies using a luciferase reporter construct expressing the IL-2 promoter or a tandem repeat of AP-1 or NF-κB, the inhibitory effect of ATRA on the IL-2 promoter and AP-1 construct was confirmed at the transcriptional level. However, the inhibitory effect in the NF-κB reporter construct was only marginal. In addition, our data demonstrated that JNK-1 is constitutively activated in Jurkat leukemia T cells expressing the Tax protein, suggesting that JNK-1 is required for Tax-induced proliferation of Jurkat leukemia cells.

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