Abstract |
The IGF-I receptor (IGF-IR) exhibits potent mitogenic, antiapoptotic, and transforming activities. Previous studies have suggested that the expression of the IGF-IR gene is negatively regulated by certain cytokines, including interferon-gamma (IFN-gamma). The potential involvement of STAT proteins in transcriptional regulation of the IGF-IR gene by IFN-gamma was addressed by transient coexpression of vectors encoding STAT1 and STAT5b, together with an IGF-IR promoter luciferase reporter, in the osteosarcoma-derived cell line Saos-2. Physical interactions between IFN-gamma-induced transcription factors and the IGF-IR promoter region were examined by electrophoretic mobility shift assays (EMSA). The results obtained indicate that the mechanism of action of IFN-gamma involves stimulation of STAT1 which, in turn, binds IFN-gamma activation sites (GAS) in the IGF-IR regulatory region, thus suppressing promoter activity. Taken together, our results suggest that the IGF-IR gene is a novel target for STAT1 action and that at least part of the inhibitory effects of STAT1 may involve repression of the strongly antiapoptotic IGF-IR gene.
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Authors | Michal Shalita-Chesner, Tova Glaser, Haim Werner |
Journal | Journal of pediatric endocrinology & metabolism : JPEM
(J Pediatr Endocrinol Metab)
Vol. 17
Issue 2
Pg. 211-8
(Feb 2004)
ISSN: 0334-018X [Print] Germany |
PMID | 15055356
(Publication Type: Journal Article)
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Chemical References |
- DNA-Binding Proteins
- Milk Proteins
- STAT1 Transcription Factor
- STAT1 protein, human
- STAT3 Transcription Factor
- STAT3 protein, human
- STAT5 Transcription Factor
- STAT5B protein, human
- Trans-Activators
- Interferon-gamma
- DNA
- Receptor, IGF Type 1
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Topics |
- Binding Sites
- Blotting, Western
- Bone Neoplasms
(genetics, metabolism)
- Cell Line, Tumor
- DNA
(biosynthesis, genetics)
- DNA-Binding Proteins
(physiology)
- Electrophoretic Mobility Shift Assay
- Gene Expression Regulation
(physiology)
- Humans
- Interferon-gamma
(metabolism)
- Milk Proteins
- Osteosarcoma
(genetics, metabolism)
- Plasmids
(genetics)
- Receptor, IGF Type 1
(biosynthesis, genetics)
- STAT1 Transcription Factor
- STAT3 Transcription Factor
- STAT5 Transcription Factor
- Trans-Activators
(physiology)
- Transfection
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