Breast Cancer Research and Treatment

, Volume 120, Issue 2, pp 327–335

Co-targeting the insulin-like growth factor I receptor enhances growth-inhibitory and pro-apoptotic effects of anti-estrogens in human breast cancer cell lines

  • Ashok K. Chakraborty
  • Allison Welsh
  • Michael P. DiGiovanna
Preclinical study

Abstract

The insulin-like growth factor I receptor (IGF1R) interacts with estrogen receptor-α (ERα) and HER2. We examined the effect of combinations of IGF1R antagonists (α-IR3, AG1024) and anti-estrogens (4-hydroxy tamoxifen, fulvestrant) in two human ER+ breast cancer cell lines: BT474 (HER2 overexpressing, IGF1R low) and MCF7 (HER2 non-overexpressing, IGF1R high). In BT474 cells, growth was inhibited by anti-estrogens, but not by IGF1R antagonists; however, adding IGF1R inhibitors to anti-estrogens enhanced growth inhibition. In MCF7 cells, growth was inhibited by IGF1R and ER antagonists and more so by their combination. In both cell lines, no single agents could induce apoptosis, but combining IGF1R inhibitors with anti-estrogens induced dramatic levels of apoptosis. IGF1R antagonists enhanced the ability of the anti-estrogens to inhibit ER transcriptional activity in BT474 cells, but not in MCF7 cells. The drug combination synergistically inhibited ER and IGF1R activity. Such combinations may be useful therapy for breast cancer.

Keywords

Estrogen receptor (ER) Insulin-like growth factor I receptor (IGF1R) Breast cancer Anti-estrogen Growth factor receptor tyrosine kinase 

Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  • Ashok K. Chakraborty
    • 1
  • Allison Welsh
    • 1
  • Michael P. DiGiovanna
    • 1
  1. 1.Departments of Internal Medicine (Section of Medical Oncology) and Pharmacology, and the Yale Cancer CenterYale University School of MedicineNew HavenUSA

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