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Nuclear IRS‐1 and cancer
Author(s) -
Reiss Krzysztof,
Del Valle Luis,
Lassak Adam,
Trojanek Joanna
Publication year - 2012
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.24019
Subject(s) - biology , estrogen receptor , nuclear receptor , irs1 , nuclear localization sequence , estrogen receptor alpha , insulin receptor , cancer research , microbiology and biotechnology , cancer , insulin , endocrinology , biochemistry , transcription factor , breast cancer , genetics , gene , nucleus , insulin resistance
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. J. Cell. Physiol. 227: 2992–3000, 2012. © 2011 Wiley Periodicals, Inc.