The activation of an extracellular signal-regulated kinase by oestradiol interferes with the effects of trastuzumab on HER2 signalling in endometrial adenocarcinoma cell lines

European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)
O TreeckOlaf Ortmann

Abstract

Cellular response to oestradiol stimuli is mediated both by oestrogen receptor (ER) binding to oestrogen response elements (EREs) and by non-nuclear actions like activation of mitogen-activated protein kinase (MAPK) signal transduction. Therefore, oestradiol stimuli might be able to interfere with the action of antitumoral substances directed against receptor tyrosine kinase signalling. We investigated the effect of oestradiol on the inhibition of HER2 signalling by trastuzumab (Herceptin) in two human endometrial adenocarcinoma cell lines. Activation of the extracellular signal-regulated kinase (ERK-1/2), a major mediator of HER2 signalling, was measured by means of western blotting experiments and ERE activation was determined in transient reporter-gene assays. In endometrial Ishikawa and HEC-1A adenocarcinoma cells, HER2 signalling was inhibited by trastuzumab only in the absence of oestradiol. We were able to demonstrate that oestradiol counteracted the inhibitory effects of trastuzumab by rapid phosphorylation of ERK-1/2, a kinase downstream of the HER2 receptor. The pure anti-oestrogen ICI 182,780 was able to restore both the trastuzumab-triggered inhibition of the ERK-1/2 pathway and the antiproliferative action of this ...Continue Reading

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Citations

Nov 7, 2012·The Breast : Official Journal of the European Society of Mastology·Aggelos LaliotisEfstathios N Stathopoulos
Jul 17, 2009·Journal of Cellular and Molecular Medicine·Susanne HippKarl-Friedrich Becker
Sep 12, 2006·Gynecologic Oncology·Kirsten EjskjaerOle Mogensen
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Oct 31, 2017·Cancer Biomarkers : Section a of Disease Markers·Lan LuoLiang Tang
Dec 8, 2017·Scandinavian Journal of Public Health·Maria KristiansenCarsten Hendriksen
Oct 2, 2021·BMC Bioinformatics·Giuseppe Agapito, Mario Cannataro

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