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.
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. Here we report both, a lack of signal transducer and activator of transcription induction in interferon-alpha resistant renal cell carcinoma cells and signal transducer and activator of transcription 1 reinduction of phorbol 12-myristate 13-acetate-stimulated peripheral blood mononuclear cells supernatant. 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. This work provides the basis for therapeutic strategies directed at the molecular modulation of interferon-alpha resistance in human neoplasms.
Brinckmann
A
A
Department of Hematology and Oncology, Medizinische Hochschule, Hannover, Germany.
Axer
S
S
Jakschies
D
D
Dallmann
I
I
Grosse
J
J
Patzelt
T
T
Bernier
T
T
Emmendoerffer
A
A
Atzpodien
J
J
D000970:Antineoplastic Agents / Q000494:pharmacology; D002292:Carcinoma, Renal Cell / Q000503:physiopathology*; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology*; D007680:Kidney Neoplasms / Q000503:physiopathology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000502:physiology*; D011994:Recombinant Proteins; D050794:STAT1 Transcription Factor; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D015534:Trans-Activators / Q000096:biosynthesis; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D015534:Trans-Activators; D013755:Tetradecanoylphorbol Acetate