{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T05:22:57Z","timestamp":1790054577046,"version":"4.0.1"},"reference-count":39,"publisher":"National Academy of Sciences","issue":"4","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2001,2,13]]},"abstract":"<jats:p>The ATM gene is mutated in the syndrome of ataxia telangiectasia\n (AT), associated with neurologic dysfunction, growth abnormalities, and\n extreme radiosensitivity. Insulin-like growth factor-I receptor\n (IGF-IR) is a cell surface receptor with tyrosine kinase activity that\n can mediate mitogenesis, cell transformation, and inhibition of\n apoptosis. We report here that AT cells express low levels of\n IGF-IR and show decreased IGF-IR promoter activity compared with\n wild-type cells. Complementation of AT cells with the ATM cDNA results\n in increased IGF-IR promoter activity and elevated IGF-IR levels,\n whereas expression in wild-type cells of a dominant negative fragment\n of ATM specifically reduces IGF-IR expression, results consistent with\n a role for ATM in regulating IGF-IR expression at the level of\n transcription. When expression of IGF-IR cDNA is forced in AT cells via\n a heterologous viral promoter, near normal radioresistance is conferred\n on the cells. Conversely, in ATM cells complemented with the ATM cDNA,\n specific inhibition of the IGF-IR pathway prevents correction of the\n radiosensitivity. Taken together, these results establish a fundamental\n link between ATM function and IGF-IR expression and suggest that\n reduced expression of IGF-IR contributes to the radiosensitivity of AT\n cells. In addition, because IGF-I plays a major role in human growth\n and metabolism and serves as a survival and differentiation factor for\n developing neuronal tissue, these results may provide a basis for\n understanding other aspects of the AT syndrome, including the growth\n abnormalities, insulin resistance, and neurodegeneration.<\/jats:p>","DOI":"10.1073\/pnas.98.4.1676","type":"journal-article","created":{"date-parts":[[2012,7,26]],"date-time":"2012-07-26T19:12:10Z","timestamp":1343329930000},"page":"1676-1681","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":139,"title":["ATM-dependent expression of the insulin-like growth factor-I receptor in a pathway regulating radiation response"],"prefix":"10.1073","volume":"98","author":[{"given":"Shani","family":"Peretz","sequence":"first","affiliation":[{"name":"Departments of Therapeutic Radiology and Genetics, Yale University\r School of Medicine, New Haven, CT 06520-8040; and Kimmel\r Cancer Center, Thomas Jefferson University, Philadelphia, PA\r 19107-5541"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Jensen","sequence":"additional","affiliation":[{"name":"Departments of Therapeutic Radiology and Genetics, Yale University\r School of Medicine, New Haven, CT 06520-8040; and Kimmel\r Cancer Center, Thomas Jefferson University, Philadelphia, PA\r 19107-5541"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renato","family":"Baserga","sequence":"additional","affiliation":[{"name":"Departments of Therapeutic Radiology and Genetics, Yale University\r School of Medicine, New Haven, CT 06520-8040; and Kimmel\r Cancer Center, Thomas Jefferson University, Philadelphia, PA\r 19107-5541"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter M.","family":"Glazer","sequence":"additional","affiliation":[{"name":"Departments of Therapeutic Radiology and Genetics, Yale University\r School of Medicine, New 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