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Nuclear IRS-1 and cancer.
- Source :
-
Journal of cellular physiology [J Cell Physiol] 2012 Aug; Vol. 227 (8), pp. 2992-3000. - Publication Year :
- 2012
-
Abstract
- The family of insulin receptor substrates (IRS) consists of four proteins (IRS-1-IRS-4), which were initially characterized as typical cytosolic adaptor proteins involved in insulin receptor (IR) and insulin-like growth factor I receptor (IGF-IR) signaling. The first cloned and characterized member of the IRS family, IRS-1, has a predicted molecular weight of 132 kDa, however, as a result of its extensive serine phosphorylation it separates on a SDS gel as a band of approximately 160-185 kDa. In addition to its metabolic and growth-promoting functions, IRS-1 is also suspected to play a role in malignant transformation. The mechanism by which IRS-1 supports tumor growth is not fully understood, and the argument that IRS-1 merely amplifies the signal from the IGF-1R and/or IR requires further investigation. Almost a decade ago, we reported the presence of nuclear IRS-1 in medulloblastoma clinical samples, which express viral oncoprotein, large T-antigen of human polyomavirus JC (JCV T-antigen). This first demonstration of nuclear IRS-1 was confirmed by several other laboratories. Nuclear IRS-1 was also detected by cells expressing the SV40 T-antigen, v-Src, in immortalized fibroblasts stimulated with IGF-I, in hepatocytes, 32D cells, and in an osteosarcoma cell line. More recently, nuclear IRS-1 was detected in breast cancer cells in association with estrogen receptor alpha (ERα), and in JC virus negative medulloblastoma cells expressing estrogen receptor beta (ERβ), further implicating nuclear IRS-1 in cellular transformation. Here, we discuss how nuclear IRS-1 acting on DNA repair fidelity, transcriptional activity, and cell growth can support tumor development and progression.<br /> (Copyright © 2011 Wiley Periodicals, Inc.)
- Subjects :
- Animals
Cell Nucleus metabolism
DNA Repair genetics
Gene Expression Regulation, Neoplastic
Humans
Insulin Receptor Substrate Proteins chemistry
Insulin-Like Growth Factor I metabolism
Mice
Neoplasms metabolism
Signal Transduction
Cell Transformation, Neoplastic genetics
Insulin Receptor Substrate Proteins genetics
Insulin Receptor Substrate Proteins metabolism
Neoplasms genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4652
- Volume :
- 227
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Journal of cellular physiology
- Publication Type :
- Academic Journal
- Accession number :
- 22454254
- Full Text :
- https://doi.org/10.1002/jcp.24019