Co-targeting ER and HER family receptors induces apoptosis in HER2-normal or overexpressing breast cancer models

Ashok K. Chakraborty, Ranee Mehra, Michael P. Digiovanna

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Estrogen receptor (ER) and human epidermal growth factor receptor (HER) family receptors interact in breast cancer; co-targeting these receptors is of interest. We previously reported on a synergistic growth inhibition for the combination of trastuzumab plus tamoxifen in HER2+/ER+ BT474 cells, but no induction of apoptosis. Herein we describe the effects of co-targeting in models of differing HER2 overexpression status (MCF7 HER2-normal/ER+, BT474 HER2-overexpressing/ER+). Materials and Methods: Assays of proliferation were carried-out using WST-1, cell cycle using flow cytometry, and apoptosis by determination of sub-G1 population and by annexin-V. Results: Combining a dual HER2/EGFR kinase inhibitor with anti-estrogens induces apoptosis of BT474 cells. Furthermore, in MCF7 cells, despite HER2-normal status and lack of response to single-agent HER2 inhibitors, addition of HER2 inhibitors or dual HER2/EGFR inhibitor to antiestrogens augments the anti proliferative effect of anti-estrogens, and converts the drug effect from cytostatic to apoptosisinducing. Conclusion: ER-HER co-targeting enhanced the antitumor effects and can bring about effects of targeting HER2 in models of HER2-normal breast cancer.

Original languageEnglish (US)
Pages (from-to)1243-1250
Number of pages8
JournalAnticancer Research
Volume35
Issue number3
StatePublished - Mar 1 2015

Keywords

  • Apoptosis
  • Breast cancer
  • EGFR
  • Estrogen receptor (ER)
  • Fulvestrant (Faslodex)
  • GW2974
  • HER2
  • Proliferation
  • Tamoxifen
  • Trastuzumab (Herceptin)

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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