Low expression of G protein-coupled oestrogen receptor 1 (GPER) is associated with adverse survival of breast cancer patients.

Stewart G Martin,Graham Ball,Andrew R Green,Emad A Rakha,Ian O Ellis,Bhudsaban Sukkarn,Sarah J Storr,Marie N Lebot

doi:10.18632/oncotarget.25408

Stewart G Martin, Graham Ball + Show 6 more

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https://doi.org/10.18632/oncotarget.25408

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Abstract

G protein-coupled oestrogen receptor 1 (GPER), also called G protein-coupled receptor 30 (GPR30), is attracting considerable attention for its potential role in breast cancer development and progression. Activation by oestrogen (17β-oestradiol; E2) initiates short term, non-genomic, signalling events both in vitro and in vivo. Published literature on the prognostic value of GPER protein expression in breast cancer indicates that further assessment is warranted. We show, using immunohistochemistry on a large cohort of primary invasive breast cancer patients (n=1245), that low protein expression of GPER is not only significantly associated with clinicopathological and molecular features of aggressive behaviour but also significantly associated with adverse survival of breast cancer patients. Furthermore, assessment of GPER mRNA levels in the METABRIC cohort (n=1980) demonstrates that low GPER mRNA expression is significantly associated with adverse survival of breast cancer patients. Using artificial neural networks, genes associated with GPER mRNA expression were identified; these included notch-4 and jagged-1. These results support the prognostic value for determination of GPER expression in breast cancer.

Highlights

Breast cancer is the most common cancer in women, with over 1.7 million cases diagnosed worldwide in 2012 [1]
Tamoxifen has been shown to act as a G protein-coupled oestrogen receptor 1 (GPER) agonist, and GPER has been implicated in tamoxifen resistance via its upregulation in a tamoxifen resistant breast cancer cell line which results in the activation of epidermal growth factor receptor (EGFR) [12]
We describe how GPER protein and mRNA expression levels at the time of surgery are associated with breast cancer patient survival and various clinicopathological variables

Summary

Introduction

Breast cancer is the most common cancer in women, with over 1.7 million cases diagnosed worldwide in 2012 [1]. G protein-coupled oestrogen receptor 1 (GPER) or G protein-coupled receptor 30 (GPR30) is a G protein-coupled receptor first cloned in 1996 [2] and first described in breast cancer in the ER positive MCF-7 cell line [3]. Expression of GPER has been shown to be associated with ER expression and status in a number of studies [11] and to attenuate the growth of ER positive breast cancer [11]. Tamoxifen has been shown to act as a GPER agonist, and GPER has been implicated in tamoxifen resistance via its upregulation in a tamoxifen resistant breast cancer cell line which results in the activation of epidermal growth factor receptor (EGFR) [12]

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