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Article

Inhibition of growth hormone receptor by Somavert reduces expression of GPER and prevents growth stimulation of triple‑negative breast cancer by 17β‑estradiol

  • Authors:
    • Rainer Girgert
    • Günter Emons
    • Carsten Gründker
  • View Affiliations / Copyright

    Affiliations: Department of Obstetrics and Gynecology, University Medical Center Goettingen, D‑37075 Goettingen, Germany
  • Pages: 9559-9566
    |
    Published online on: April 18, 2018
       https://doi.org/10.3892/ol.2018.8521
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Abstract

Currently, conventional chemotherapy is the only treatment option for triple‑negative breast cancers (TNBC) due to a lack of a unique target. In TNBC, a high expression of the membrane bound G protein‑coupled estrogen receptor (GPER), correlates with a worse outcome. There is a potential for an association between growth hormone receptor (GHR) and GPER expression. To confirm this hypothesis, GHR was inhibited in TNBC cells with Somavert, and GPER expression levels, and the effect on signal transduction and proliferation induction in TNBC cells were analyzed. Proliferation of TNBC cells was measured using an Alamar‑blue assay. Expression of GPER and activation of c‑src and epidermal growth factor receptor (EGFR) by 17β‑estradiol was analyzed by western blotting. Induction of c‑fos, cyclin D1 and aromatase expression was determined by reverse transcription‑semi‑quantitative polymerase chain reaction. The expression of GPER was concentration‑ and time‑dependently reduced by Somavert down to 46±7% (P<0.01) of the control. Furthermore, 17β‑estradiol significantly increased the cell number of HCC1806 cells to 128±14% (P<0.05), and that of MDA‑MB‑453 cells to 115±3%. This increase in cell number was reduced to 103±11% in HCC1806 cells in which GPER expression was downregulated by Somavert, and to 102±3% in MDA‑MB‑453 cells. In addition, 17β‑estradiol increased the activation of c‑src in HCC1806 cells by 1.8‑fold, and Somavert reduced p‑src to 63% of control. In MDA‑MB‑453 cells src phosphorylation increased by 7‑fold upon stimulation with estradiol, but after treatment with Somavert only a 4‑fold increase was observed. Phosphorylation of EGFR was increased by 2.2‑fold of control in HCC1806 cells by 17β‑estradiol, and by 1.4‑fold in MDA‑MD‑453 cells. Somavert completely prevented this activation. Induction of cyclin D1 and aromatase expression by 17β‑estradiol was also prevented by Somavert. Somavert reduces GPER expression in triple negative breast cancer cells. Treatment with Somavert prevents induction of genes regulating proliferation by 17β‑estradiol. Inhibition of GPER expression is a promising therapeutic intervention for TNBC.
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Copy and paste a formatted citation
Spandidos Publications style
Girgert R, Emons G and Gründker C: Inhibition of growth hormone receptor by Somavert reduces expression of GPER and prevents growth stimulation of triple‑negative breast cancer by 17β‑estradiol . Oncol Lett 15: 9559-9566, 2018.
APA
Girgert, R., Emons, G., & Gründker, C. (2018). Inhibition of growth hormone receptor by Somavert reduces expression of GPER and prevents growth stimulation of triple‑negative breast cancer by 17β‑estradiol . Oncology Letters, 15, 9559-9566. https://doi.org/10.3892/ol.2018.8521
MLA
Girgert, R., Emons, G., Gründker, C."Inhibition of growth hormone receptor by Somavert reduces expression of GPER and prevents growth stimulation of triple‑negative breast cancer by 17β‑estradiol ". Oncology Letters 15.6 (2018): 9559-9566.
Chicago
Girgert, R., Emons, G., Gründker, C."Inhibition of growth hormone receptor by Somavert reduces expression of GPER and prevents growth stimulation of triple‑negative breast cancer by 17β‑estradiol ". Oncology Letters 15, no. 6 (2018): 9559-9566. https://doi.org/10.3892/ol.2018.8521
Copy and paste a formatted citation
x
Spandidos Publications style
Girgert R, Emons G and Gründker C: Inhibition of growth hormone receptor by Somavert reduces expression of GPER and prevents growth stimulation of triple‑negative breast cancer by 17β‑estradiol . Oncol Lett 15: 9559-9566, 2018.
APA
Girgert, R., Emons, G., & Gründker, C. (2018). Inhibition of growth hormone receptor by Somavert reduces expression of GPER and prevents growth stimulation of triple‑negative breast cancer by 17β‑estradiol . Oncology Letters, 15, 9559-9566. https://doi.org/10.3892/ol.2018.8521
MLA
Girgert, R., Emons, G., Gründker, C."Inhibition of growth hormone receptor by Somavert reduces expression of GPER and prevents growth stimulation of triple‑negative breast cancer by 17β‑estradiol ". Oncology Letters 15.6 (2018): 9559-9566.
Chicago
Girgert, R., Emons, G., Gründker, C."Inhibition of growth hormone receptor by Somavert reduces expression of GPER and prevents growth stimulation of triple‑negative breast cancer by 17β‑estradiol ". Oncology Letters 15, no. 6 (2018): 9559-9566. https://doi.org/10.3892/ol.2018.8521
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