ATM-dependent expression of the insulin-like growth factor-I receptor in a pathway regulating radiation response
| العنوان: | ATM-dependent expression of the insulin-like growth factor-I receptor in a pathway regulating radiation response |
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| المؤلفون: | Renato Baserga, Peter M. Glazer, Ryan B. Jensen, Shani Peretz |
| المصدر: | Proceedings of the National Academy of Sciences. 98:1676-1681 |
| بيانات النشر: | Proceedings of the National Academy of Sciences, 2001. |
| سنة النشر: | 2001 |
| مصطلحات موضوعية: | DNA, Complementary, Cell Survival, medicine.medical_treatment, Cell Cycle Proteins, Ataxia Telangiectasia Mutated Proteins, Protein Serine-Threonine Kinases, Biology, Receptor, IGF Type 1, Cell surface receptor, Radioresistance, medicine, Humans, Radiosensitivity, Promoter Regions, Genetic, Cell Line, Transformed, Regulation of gene expression, Leucine Zippers, Multidisciplinary, Tumor Suppressor Proteins, Growth factor, Biological Sciences, medicine.disease, Cell biology, DNA-Binding Proteins, Gene Expression Regulation, Ataxia-telangiectasia, Tyrosine kinase |
| الوصف: | The ATM gene is mutated in the syndrome of ataxia telangiectasia (AT), associated with neurologic dysfunction, growth abnormalities, and extreme radiosensitivity. Insulin-like growth factor-I receptor (IGF-IR) is a cell surface receptor with tyrosine kinase activity that can mediate mitogenesis, cell transformation, and inhibition of apoptosis. We report here that AT cells express low levels of IGF-IR and show decreased IGF-IR promoter activity compared with wild-type cells. Complementation of AT cells with the ATM cDNA results in increased IGF-IR promoter activity and elevated IGF-IR levels, whereas expression in wild-type cells of a dominant negative fragment of ATM specifically reduces IGF-IR expression, results consistent with a role for ATM in regulating IGF-IR expression at the level of transcription. When expression of IGF-IR cDNA is forced in AT cells via a heterologous viral promoter, near normal radioresistance is conferred on the cells. Conversely, in ATM cells complemented with the ATM cDNA, specific inhibition of the IGF-IR pathway prevents correction of the radiosensitivity. Taken together, these results establish a fundamental link between ATM function and IGF-IR expression and suggest that reduced expression of IGF-IR contributes to the radiosensitivity of AT cells. In addition, because IGF-I plays a major role in human growth and metabolism and serves as a survival and differentiation factor for developing neuronal tissue, these results may provide a basis for understanding other aspects of the AT syndrome, including the growth abnormalities, insulin resistance, and neurodegeneration. |
| تدمد: | 1091-6490 0027-8424 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b6d67e0174666f65238d37f346198533 https://doi.org/10.1073/pnas.98.4.1676 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....b6d67e0174666f65238d37f346198533 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10916490 00278424 |
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