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Insulin Receptor Substrates (IRSs) and Breast Tumorigenesis

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Journal of Mammary Gland Biology and Neoplasia Aims and scope Submit manuscript

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.

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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

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Acknowledgements

We thank Dr Robert K. Dearth for reading the manuscript and giving useful comments. Dr Bonita Tak-Yee Chan is supported by the Diana Helis Henry Medical Research Foundation. Dr Adrian V. Lee’s research is supported in part by grant R01CA94118 from the NIH/NCI.

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Authors and Affiliations

  1. Lester and Sue Smith Breast Center, Department of Medicine and Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA

    Bonita Tak-Yee Chan & Adrian V. Lee

  2. Breast Center, Baylor College of Medicine, One Baylor Plaza, MS:600, Room N1110, Houston, TX, 77030, USA

    Adrian V. Lee

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  1. Bonita Tak-Yee Chan
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Chan, B.TY., Lee, A.V. Insulin Receptor Substrates (IRSs) and Breast Tumorigenesis. J Mammary Gland Biol Neoplasia 13, 415–422 (2008). https://doi.org/10.1007/s10911-008-9101-9

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  • DOI: https://doi.org/10.1007/s10911-008-9101-9

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