Abstract | BACKGROUND: METHODS: Functional receptors were characterized using ligand-binding studies, second-messenger activation and determination of ligand-mediated growth effects. STAT protein activation was analysed by electrophoretic mobility shift assay (EMSA) using labelled DNA response elements recognizing all known STAT proteins. RESULTS: Functional bombesin receptors mediating mitogenic effects were demonstrated on Swiss 3T3 fibroblasts, human melanoma cells (A375-6) and primary human lung fibroblasts; however, bombesin-related STAT protein activation was not observed by EMSA. Interferon-alpha typically activated a STAT1-STAT2-p48 heterotrimer, as well as STAT1-3 hetero- and homodimers in human melanoma cells and significantly inhibited growth of this cell line in vitro. Functional AT1A receptors on primary rat cardiac fibroblasts mediated angiotensin-stimulated growth effects but, in contrast to recently published data, did not activate any known STAT protein. CONCLUSION:
Interferon alpha-stimulated growth inhibition is mediated by activation of the Jak/STAT pathway, whereas bombesin or AT1A receptor-mediated effects on cellular proliferation do not involve phosphorylation of STAT proteins.
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Authors | A Pansky, P Hildebrand, M H Heim, M Eberhard, T Kissel, C Beglinger |
Journal | European journal of clinical investigation
(Eur J Clin Invest)
Vol. 28
Issue 5
Pg. 398-406
(May 1998)
ISSN: 0014-2972 [Print] England |
PMID | 9650014
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- DNA-Binding Proteins
- Growth Inhibitors
- Interferon-alpha
- STAT1 Transcription Factor
- STAT1 protein, human
- STAT2 Transcription Factor
- STAT2 protein, human
- STAT3 Transcription Factor
- STAT3 protein, human
- Stat1 protein, mouse
- Stat1 protein, rat
- Stat2 protein, mouse
- Stat3 protein, mouse
- Stat3 protein, rat
- Trans-Activators
- Angiotensin II
- Bombesin
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Topics |
- 3T3 Cells
- Angiotensin II
(pharmacology)
- Animals
- Bombesin
(pharmacology)
- Cell Division
(drug effects)
- DNA-Binding Proteins
(metabolism)
- Fibroblasts
(drug effects)
- Growth Inhibitors
(pharmacology)
- Humans
- Interferon-alpha
(pharmacology)
- Lung
(cytology)
- Melanoma
(pathology)
- Mice
- Myocardium
(cytology)
- Rats
- STAT1 Transcription Factor
- STAT2 Transcription Factor
- STAT3 Transcription Factor
- Signal Transduction
(drug effects)
- Trans-Activators
(metabolism)
- Tumor Cells, Cultured
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