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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.

Brinckmann A, Axer S, Jakschies D, Dallmann I, Grosse J, Patzelt T, Bernier T, Emmendoerffer A, Atzpodien J - Br. J. Cancer (2002)

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Hematology and Oncology, Medizinische Hochschule, Hannover, Germany.

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Electrophoretic mobility shift assays for STAT1 induction by 10 ng ml−1 PMA. (A) STAT1 induction in IFN-α sensitive (S) A-498 cells by 10 ng ml−1 PMA. Cells were either left untreated (lane 1) or were treated with IFN-α alone (lane 2) or PMA alone (lanes 3, 5, 7 and 9) or with their combination (lanes 4, 6, 8 and 10). STAT1 indiction can be detected after incubation with IFN-α alone (lane 2) and in combination with PMA (lanes 4, 6, 8 and 10). PMA alone does not induce STAT1 (lanes 3, 5, 7, 9) (see arrow for STAT1 band). (B) STAT1 induction in IFN-α resistant (R) A-498 cells by 10 ng ml−1 PMA. Cells were either left untreated (lane 2) or were treated with IFN-α alone (lane 3) or PMA alone (lanes 4, 6, 8 and 10) or with their combination (lanes 5, 7, 9 and 11). IFN-α and PMA alone as well as their combination fail to induce STAT1 in resistant cells. IFN-α treated A-498 S cells were used as positive control (lane 1) (see arrow for STAT1 band).
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fig6: Electrophoretic mobility shift assays for STAT1 induction by 10 ng ml−1 PMA. (A) STAT1 induction in IFN-α sensitive (S) A-498 cells by 10 ng ml−1 PMA. Cells were either left untreated (lane 1) or were treated with IFN-α alone (lane 2) or PMA alone (lanes 3, 5, 7 and 9) or with their combination (lanes 4, 6, 8 and 10). STAT1 indiction can be detected after incubation with IFN-α alone (lane 2) and in combination with PMA (lanes 4, 6, 8 and 10). PMA alone does not induce STAT1 (lanes 3, 5, 7, 9) (see arrow for STAT1 band). (B) STAT1 induction in IFN-α resistant (R) A-498 cells by 10 ng ml−1 PMA. Cells were either left untreated (lane 2) or were treated with IFN-α alone (lane 3) or PMA alone (lanes 4, 6, 8 and 10) or with their combination (lanes 5, 7, 9 and 11). IFN-α and PMA alone as well as their combination fail to induce STAT1 in resistant cells. IFN-α treated A-498 S cells were used as positive control (lane 1) (see arrow for STAT1 band).

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


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.

Brinckmann A, Axer S, Jakschies D, Dallmann I, Grosse J, Patzelt T, Bernier T, Emmendoerffer A, Atzpodien J - Br. J. Cancer (2002)

Electrophoretic mobility shift assays for STAT1 induction by 10 ng ml−1 PMA. (A) STAT1 induction in IFN-α sensitive (S) A-498 cells by 10 ng ml−1 PMA. Cells were either left untreated (lane 1) or were treated with IFN-α alone (lane 2) or PMA alone (lanes 3, 5, 7 and 9) or with their combination (lanes 4, 6, 8 and 10). STAT1 indiction can be detected after incubation with IFN-α alone (lane 2) and in combination with PMA (lanes 4, 6, 8 and 10). PMA alone does not induce STAT1 (lanes 3, 5, 7, 9) (see arrow for STAT1 band). (B) STAT1 induction in IFN-α resistant (R) A-498 cells by 10 ng ml−1 PMA. Cells were either left untreated (lane 2) or were treated with IFN-α alone (lane 3) or PMA alone (lanes 4, 6, 8 and 10) or with their combination (lanes 5, 7, 9 and 11). IFN-α and PMA alone as well as their combination fail to induce STAT1 in resistant cells. IFN-α treated A-498 S cells were used as positive control (lane 1) (see arrow for STAT1 band).
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Related In: Results  -  Collection

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fig6: Electrophoretic mobility shift assays for STAT1 induction by 10 ng ml−1 PMA. (A) STAT1 induction in IFN-α sensitive (S) A-498 cells by 10 ng ml−1 PMA. Cells were either left untreated (lane 1) or were treated with IFN-α alone (lane 2) or PMA alone (lanes 3, 5, 7 and 9) or with their combination (lanes 4, 6, 8 and 10). STAT1 indiction can be detected after incubation with IFN-α alone (lane 2) and in combination with PMA (lanes 4, 6, 8 and 10). PMA alone does not induce STAT1 (lanes 3, 5, 7, 9) (see arrow for STAT1 band). (B) STAT1 induction in IFN-α resistant (R) A-498 cells by 10 ng ml−1 PMA. Cells were either left untreated (lane 2) or were treated with IFN-α alone (lane 3) or PMA alone (lanes 4, 6, 8 and 10) or with their combination (lanes 5, 7, 9 and 11). IFN-α and PMA alone as well as their combination fail to induce STAT1 in resistant cells. IFN-α treated A-498 S cells were used as positive control (lane 1) (see arrow for STAT1 band).
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

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Hematology and Oncology, Medizinische Hochschule, Hannover, Germany.

Show MeSH
Related in: MedlinePlus