Interferon-alpha resistance in renal carcinoma cells is associated with defective induction of signal transducer and activator of transcription 1 which can be restored by a supernatant of phorbol 12-myristate 13-acetate stimulated peripheral blood mononuclear cells.
Bottom Line: Therapy of selected human malignancies with interferon-alpha is widely accepted but often complicated by the emergence of interferon-alpha resistance.Interferon is a pleiotropic cytokine with antiproliferative, antitumour, antiviral and immunmodulatory effect; it signals through the Jak-STAT signal transduction pathway where signal transducer and activator of transcription 1 plays an important role.Preliminary experiments on the identification of the molecules that reinducing signal transducers and activators of transcription 1 indicate that interferon-gamma may be the responsible candidate cytokine, but several others may be involved as well.
Affiliation: Department of Hematology and Oncology, Medizinische Hochschule, Hannover, Germany.Show MeSH
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Mentions: In order to demonstrate that the effect of STAT1 reinduction was due to the cytokines secreted by PMA-stimulated PBMC and not by PMA itself, A-498 cells were incubated with 10 ng ml−1 of PMA either alone and in combination with IFN-α. PMA alone did not induce STAT1 neither in the sensitive nor in the resistant cells, while the combination of PMA and IFN-α induced STAT1 in the sensitive cells, but not in the resistant cells (Figure 6A,BFigure 6
Affiliation: Department of Hematology and Oncology, Medizinische Hochschule, Hannover, Germany.