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Open Access Highly Accessed Research article

Enhanced expression of G-protein coupled estrogen receptor (GPER/GPR30) in lung cancer

Venkatakrishna Rao Jala1*, Brandie N Radde2, Bodduluri Haribabu1 and Carolyn M Klinge2

Author Affiliations

1 James Graham Brown Cancer Center, Department of Microbiology and Immunology, 505 South Hancock Street, Room 323, CTR Building, Louisville, KY 40202, USA

2 Department of Biochemistry and Molecular Biology, and Center for Genetics and Molecular Medicine, University of Louisville School of Medicine, Louisville, KY, 40202, USA

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BMC Cancer 2012, 12:624  doi:10.1186/1471-2407-12-624

Published: 28 December 2012

Abstract

Background

G-protein-coupled estrogen receptor (GPER/GPR30) was reported to bind 17β-estradiol (E2), tamoxifen, and ICI 182,780 (fulvestrant) and promotes activation of epidermal growth factor receptor (EGFR)-mediated signaling in breast, endometrial and thyroid cancer cells. Although lung adenocarcinomas express estrogen receptors α and β (ERα and ERβ), the expression of GPER in lung cancer has not been investigated. The purpose of this study was to examine the expression of GPER in lung cancer.

Methods

The expression patterns of GPER in various lung cancer lines and lung tumors were investigated using standard quantitative real time PCR (at mRNA levels), Western blot and immunohistochemistry (IHC) methods (at protein levels). The expression of GPER was scored and the pairwise comparisons (cancer vs adjacent tissues as well as cancer vs normal lung tissues) were performed.

Results

Analysis by real-time PCR and Western blotting revealed a significantly higher expression of GPER at both mRNA and protein levels in human non small cell lung cancer cell (NSCLC) lines relative to immortalized normal lung bronchial epithelial cells (HBECs). The virally immortalized human small airway epithelial cell line HPL1D showed higher expression than HBECs and similar expression to NSCLC cells. Immunohistochemical analysis of tissue sections of murine lung adenomas as well as human lung adenocarcinomas, squamous cell carcinomas and non-small cell lung carcinomas showed consistently higher expression of GPER in the tumor relative to the surrounding non-tumor tissue.

Conclusion

The results from this study demonstrate increased GPER expression in lung cancer cells and tumors compared to normal lung. Further evaluation of the function and regulation of GPER will be necessary to determine if GPER is a marker of lung cancer progression.

Keywords:
GPER; GPR30; Estrogen; Estrogen receptor; Lung cancer; Protein expression; Immunohistochemistry; Tissue microarray