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p53 regulates insul...
p53 regulates insulin-like growth factor-I (IGF-I) receptor expression and IGF-I-induced tyrosine phosphorylation in an osteosarcoma cell line: interaction between p53 and Sp1.
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- Ohlsson, Claes, 1965 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för invärtesmedicin, Avdelningen för internmedicin,Institute of Internal Medicine, Dept of Medicine
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Kley, N (författare)
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Werner, H (författare)
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visa fler...
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LeRoith, D (författare)
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visa färre...
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(creator_code:org_t)
- 1998
- 1998
- Engelska.
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Ingår i: Endocrinology. - 0013-7227. ; 139:3, s. 1101-7
- Relaterad länk:
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https://gup.ub.gu.se...
Abstract
Ämnesord
Stäng
- The insulin-like growth factor-I receptor (IGF-IR) is involved in tumorigenesis. The aim of the present study was to investigate whether the IGF-IR is a physiological target for p53 in osteosarcoma cells. The p53-induced regulation of IGF-IR levels was studied in a tetracycline-regulated expression system. When expressed in Saos-2, osteosarcoma cells that lack p53, wild-type p53 decreased, whereas mutated p53 increased IGF-IR expression, and IGF-I-induced tyrosine phosphorylation of the IGF-IR. Similarly, wild-type p53 decreased IGF-I-induced tyrosine phosphorylation of IRS-1. A functional and physical interaction between p53 and Sp1, in the regulation of the IGF-R, was studied in osteosarcoma cells. Expression of p53 decreased IGF-IR promoter activity, whereas no effect on promoter activity was seen by Sp1 expressed alone. However, Sp1 counteracted the inhibitory effect of p53 on IGF-IR promoter activity in a dose-dependent manner. Furthermore, wild-type and mutated p53 were coimmunoprecipitated with Sp1, indicating a physical interaction between p53 and Sp1. In conclusion, p53 regulates IGF-IR expression, as reflected by a reduction in IGF-IR protein and a parallel reduction in IGF-I-induced tyrosine phosphorylation of the IGF-IR and IRS-1 in an osteosarcoma cell line. These data indicate that the IGF-I receptor is a physiological target for p53 in osteosarcoma cells. Furthermore, data supporting an interaction between p53 and Sp1 in the regulation of the promoter activity of IGF-IR are presented.
Nyckelord
- Humans
- Insulin-Like Growth Factor I
- pharmacology
- Mutation
- Osteosarcoma
- metabolism
- Phosphorylation
- Promoter Regions
- Genetic
- Receptor
- IGF Type 1
- analysis
- genetics
- Sp1 Transcription Factor
- physiology
- Tumor Cells
- Cultured
- Tumor Suppressor Protein p53
- physiology
- Tyrosine
- metabolism
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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