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Crosstalk Between IGF1R and Estrogen Receptor Signaling in Breast Cancer

  • Dedra H. Fagan
  • Douglas YeeEmail author
Article

Abstract

After the discovery that depriving certain breast tumors of estrogen promoted tumor regression, therapeutic strategies aimed at depriving tumors of this hormone were developed. The tumorigenic properties of estrogen are regulated through the estrogen receptor-α (ER), making understanding the mechanisms that activate this receptor highly relevant. In addition to estrogen activating the ER, other growth factor pathways, such as the insulin-like growth factors (IGFs), can activate the ER. This review will examine the interaction between these two pathways. Estrogen can activate the growth stimulatory properties of the IGF pathway via ER’s genomic and non-genomic functions. Further, blockade of ER function can inhibit IGF-mediated mitogenesis and blocking IGF action can inhibit estrogen stimulation of breast cancer cells. Collectively, these observations suggest that the two growth regulatory pathways are tightly linked and a more thorough understanding of the mechanism of this crosstalk could lead to improved therapeutic strategies in breast cancer.

Keywords

Breast cancer Estrogen receptor Insulin-like growth factors 

Abbreviations

ER

estrogen receptor

IGF

insulin-like growth factor

IGF1R

type 1 insulin-like growth factor receptor

EGF

epidermal growth factor

EGFR

epidermal growth factor receptor

MAPK

mitogen activated protein kinase

SRC

steroid receptor co-activator

IRS

insulin receptor substrate

ERE

estrogen response element

SERM

selective estrogen receptor modulator

PI3K

PI3 kinase

IGFBP

IGF-binding protein

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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  1. 1.Department of Pharmacology, Masonic Cancer CenterUniversity of MinnesotaMinneapolisUSA
  2. 2.Department of MedicineUniversity of MinnesotaMinneapolisUSA
  3. 3.MinneapolisUSA

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