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: Electrophoretic mobility shift assays for IFN-α induced STAT1 induction. IFN-α sensitive (S) and IFN-α resistant (R) A-498 and fresh RCC cells and Caki-2 cells were either left untreated or incubated with 1000 IU ml−1 IFN-α for 30 min. Lanes 1–5 are A-498 cells: lanes 1 and 4, untreated IFN-α sensitive and resistant cells, respectively; lanes 2, 3 and 5, IFN-α stimulated IFN-α sensitive and resistant cells, respectively. Lanes 6 and 7 are Caki-2 cells: lane 6, untreated Caki-2 cells; lane 7, IFN-α stimulated cells. Lanes 8–11 are fresh RCC cells: lanes 8 and 10, untreated IFN-α sensitive and resistant cells, respectively; lanes 9 and 11, IFN-α stimulated IFN-α sensitive and resistant cells, respectively. STAT1 induction can be detected in sensitive A-498 and fresh RCC cells after stimulation with IFN-α but not in resistant cells (lanes 2 and 9). STAT1 can be competed with monoclonal anti-STAT1 antibody (lane 3) (see arrow for STAT1 band).
Affiliation: Department of Hematology and Oncology, Medizinische Hochschule, Hannover, Germany.