Signal transducer and activator of transcription-1 (STAT1), but not STAT5b, regulates IGF-I receptor gene expression in an osteosarcoma cell line.

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.
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)
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
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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