The IGF-I/IGF-I Receptor Pathway: Implications in the Pathophysiology of Thyroid Cancer
Consistent with this role, it has been well established that IGF-I can protect cells from apoptosis under a variety of circumstances. For example, IGF-I prevents apoptosis induced by overexpression of c-myc in fibroblasts, by interleukin-3 withdrawal in interleukin-3-dependent hemopoietic cells, etoposide, a topoisomerase I inhibitor, anti-cancer drugs, UV-B irradiations, and serum deprivation.
While the anti-apoptotic effect of IGF-I has been clearly demonstrated, the molecular mechanisms by which IGF-I inhibits apoptosis induced by these various stimuli remain unknown.
We have previously documented increased IGF-I and IGF-I R immunoreactivity in human thyroid carcinomas with a corresponding up-regulation of IGF-I mRNA. Immunoreactivity for IGF-I and IGF-I R positively correlated with tumor diameter, but not with the occurrence of lymph node metastases. Several recent studies have identified new signaling pathways emanating from the IGF-I R that affect cancer cell proliferation, adhesion, migration and apoptosis, which represent critical functions for cancer cell survival and metastasizing capacity. In this review, various aspects of the IGFI/ IGF-I R pathway and its relationship to thyroid cancer are discussed.
Document Type: Review Article
Affiliations: Section of Internal Medicine, Endocrinology and Metabolic Disease, Department of Emergency and Organ Transplantation, University of Bari, School of Medicine, Piazza Giulio Cesare, 11, 70124 Bari, Italy.
Publication date: 2005-11-01
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