Loss of PTEN selectively desensitizes upstream IGF1 and insulin signaling

摘要: Many tumors have chronically elevated activity of PI 3-kinase-dependent signaling pathways, caused largely by oncogenic mutation 3-kinase itself or loss the opposing tumor suppressor lipid phosphatase, PTEN. Several feedback mechanisms been identified that may affect sensitivity upstream receptor signaling, but events required to initiate an inhibited state not addressed. We show in a variety cell types, PTEN via experimental knockdown lines correlates with block insulin-like growth factor 1 (IGF1)/insulin without affecting platelet-derived epidermal signaling. These effects on IGF/insulin include reduction up five- tenfold IGF-stimulated activation, failure activate ERK kinases and, some cells, reduced expression insulin substrate 1, and both IGF1 receptors. data indicate degree seen many causes selective IGF1/insulin could significantly reduce advantage deregulated activation IGF1/IGF1-R development.