Nucleus of Human Tumor Cells

Downlo type 1 insulin-like growth factor receptor (IGF-1R) is a transmembrane glycoprotein composed of two ellular α subunits and two β subunits with tyrosine kinase activity. The IGF-1R is frequently upregulated cers and signals from the cell surface to promote proliferation and cell survival. Recent attention has d on the IGF-1R as a target for cancer treatment. Here, we report that the nuclei of human tumor cells n IGF-1R, detectable using multiple antibodies to αand β-subunit domains. Cell-surface IGF-1R transs to the nucleus following clathrin-mediated endocytosis, regulated by IGF levels. The IGF-1R is unusual transmembrane receptors that undergo nuclear import, in that both α and β subunits traffic to the s. Nuclear IGF-1R is phosphorylated in response to ligand and undergoes IGF-induced interaction with atin, suggesting direct engagement in transcriptional regulation. The IGF dependence of these phenomdicates a requirement for the receptor kinase, and indeed, IGF-1R nuclear import and chromatin binding blocked by a novel IGF-1R kinase inhibitor. Nuclear IGF-1R is detectable in primary renal cancer cells, lin-fixed tumors, preinvasive lesions in the breast, and nonmalignant tissues characterized by a high ration rate. In clear cell renal cancer, nuclear IGF-1R is associated with adverse prognosis. Our findings prolife suggest that IGF-1R nuclear import has biological significance, may contribute directly to IGF-1R function, and may influence the efficacy of IGF-1R inhibitory drugs. Cancer Res; 70(16); 6412–9. ©2010 AACR.