Kortylewski, M. and Komyod, W. and Kauffmann, M. E. and Bosserhoff, Anja and Heinrich, P. C. and Behrmann, Iris (2004) Interferon-gamma-mediated growth regulation of melanoma cells: Involvement of STAT1-dependent and STAT1-independent signals. JOURNAL OF INVESTIGATIVE DERMATOLOGY, 122 (2). pp. 414-422. ISSN 0022-202X, 1523-1747
Full text not available from this repository. (Request a copy)Abstract
Interferon-gamma, a known inhibitor of tumor cell growth, has been used in several protocols for the treatment of melanoma. We have studied the molecular events underlying interferon-gamma-induced G(0)/G(1) arrest in four metastatic melanoma cell lines with different responsiveness to interferon-gamma. The growth arrest did not result from enhanced expression of cyclin-dependent kinase inhibitors p21 and p27. Instead, it correlated with downregulation of cyclin E and cyclin A and inhibition of their associated kinase activities. We show that interferon-gamma-induced growth inhibition could be abrogated by overexpression of dominant negative STAT1 (signal transducer and activator of transcription 1) in the melanoma cell line A375, suggesting that STAT1 plays a crucial part for the anti-proliferative effect. Erythropoietin stimulation of a chimeric receptor led to a concentration-dependent STAT1 activation and concomitant growth arrest when it contained the STAT recruitment motif Y440 of the interferon-gamma receptor 1. In contrast, dose-response studies for interferon-gamma revealed a discrepancy between levels of STAT1 activation and the extent of growth inhibition; whereas STAT1 was activated by low doses of interferon-gamma (10 U per mL), growth inhibitory effects were only visible with 100-fold higher concentrations. Our results suggest the presence of additional signals emanating from the interferon-gamma receptor, which may counteract the anti-proliferative function of STAT1.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CYCLIN-DEPENDENT KINASE; MAMMARY EPITHELIAL-CELLS; IFN-GAMMA; ONCOSTATIN-M; INHIBITOR P21(WAF1/CIP1); ISGF3 COMPONENTS; GENE-EXPRESSION; UP-REGULATION; FACTOR-I; C-MYC; cell cycle; chimeric receptor; cytokine resistance; cytokines; signal transduction |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 02 Aug 2021 08:32 |
| Last Modified: | 02 Aug 2021 08:32 |
| URI: | https://pred.uni-regensburg.de/id/eprint/38037 |
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