Journal of Mammary Gland Biology and Neoplasia

, Volume 13, Issue 4, pp 415–422

Insulin Receptor Substrates (IRSs) and Breast Tumorigenesis

Article

DOI: 10.1007/s10911-008-9101-9

Cite this article as:
Chan, B.TY. & Lee, A.V. J Mammary Gland Biol Neoplasia (2008) 13: 415. doi:10.1007/s10911-008-9101-9

Abstract

Insulin receptor substrate (IRS)-1 and IRS-2 are adaptor proteins in the insulin-like growth factor I (IGF-I)/IGF-I receptor (IGF-IR) pathway that mediate cell proliferation, migration, and survival. In addition to their role as scaffolding proteins in the cytoplasm, they are able to translocate into the nucleus and regulate gene transcription. IRS levels are developmentally and hormonally regulated in the normal mammary gland and both are essential for normal mammary gland bud formation and lactation. Both IRS-1 and IRS-2 are transforming oncogenes, and induce transformation and metastasis in vitro and in vivo. In breast cancer IRSs have unique functions, with IRS-1 being mainly involved in cell proliferation and survival, whereas IRS-2 has clear roles in cell migration and metastasis. In this review we will discuss the roles of IRSs in mammary gland development and breast cancer.

Keywords

Insulin receptor substrateIRS-1IRS-2IRS1IRS2Mammary glandTumorigenesisBreast cancerTransformationTransgenic mice

Abbreviations

IRS

Insulin receptor substrate

IGF-I

Insulin-like growth factor I

IGF-IR

Insulin-like growth factor I receptor

IR

Insulin receptor

PH

Plextrin homology

PTB

Phosphotyrosine binding

SH2

Src-homology 2

ER

Estrogen receptor

ERE

Estrogen-responsive element

TEB

Terminal end bud

MEF

Mouse embryo fibroblast

EGFR

Epidermal growth factor receptor

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  1. 1.Lester and Sue Smith Breast Center, Department of Medicine and Department of Molecular and Cellular BiologyBaylor College of MedicineHoustonUSA
  2. 2.Breast CenterBaylor College of MedicineHoustonUSA