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Chakraborty AK, Mehra R, Digiovanna MP
Co-targeting ER and HER family receptors induces apoptosis in HER2-normal or overexpressing breast cancer models
Anticancer Res (2015) 35:1243-50.
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 anti-estrogens augments the antiproliferative effect of anti-estrogens, and converts the drug effect from cytostatic to apoptosis-inducing. CONCLUSION: ER-HER co-targeting enhanced the antitumor effects and can bring about effects of targeting HER2 in models of HER2-normal breast cancer.
Publication Date: 2015-03-01.
Last updated on Saturday, August 22, 2020