The Correlation between GPR30 and Clinicopathologic Variables in Breast Carcinomas

Tu, Gang; Hu, Dingrong; Yang, Guanglun; Yu, Tinghe

doi:10.1177/153303460900800308

Cited by 14 publications

(11 citation statements)

References 16 publications

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“…GPER expression was positively associated with tumor size, HER2 immunohistochemical scores and distant metastasis in their report, suggesting that GPER may be involved in breast cancer progression. In the present series, GPER had no significant influence on the tumor size, consistent with Kuo et al [13] and our previous report [14] in Chinese but Filardo's [10] observations in Americans. Thus, racial differences may contribute to the discrepancy.…”

Section: Discussionsupporting

confidence: 93%

“…However, only four clinical studies [10,13-15], which included large sample populations have focused on GPER in primary breast cancers. We detected GPER by immunohistochemistry in 241 primary breast cancers to correlate its expression to clinicopathological determinants, resulting in some significant associations [14]. To further evaluate GPER in breast cancers, we expanded the sample size, collected more details of the tumors in the present paper.…”

Section: Discussionmentioning

confidence: 99%

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G-protein Coupled Estrogen Receptor 1 Expression in Primary Breast Cancers and Its Correlation with Clinicopathological Variables

Luo

Yang

et al. 2011

J Breast Cancer

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PurposeG-protein coupled estrogen receptor 1 (GPER) probably play important roles in the progression of breast cancer including endocrine therapeutic resistance. We evaluated GPER in primary breast cancers.MethodsImmunohistochemistry was used to detect GPER in paraffin-embedded tissues of primary breast cancers from 423 patients and GPER expression was correlated with clinicopathological factors.ResultsGPER was expressed in 63.8% of specimens, coexpressed with estrogen receptor alpha (ERα) in 36.6% of tumors and was positive in 62.5% of the ERα-negative tumors. The expression of GPER had no relationship with the status of ERα, progesterone receptor and HER2. Although the expression of GPER was significantly inversely related with nodal status (p=0.045), no correlation between GPER expression and other clinicopathological variables (age, menstruation status, tumor size, stage, histologic grade, Nottingham Prognostic Index or pathological type) was found.ConclusionGPER and ERα exhibited independent expression pattern of distribution in primary breast cancers. A long-term follow-up and a more definite molecular phenotype for ER are necessary in confirming studies.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

G-protein Coupled Estrogen Receptor 1 Expression in Primary Breast Cancers and Its Correlation with Clinicopathological Variables

Luo

Yang

et al. 2011

J Breast Cancer

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“…GPER is an E 2 binding, G-protein coupled membrane receptor [39-42,58] that was reported to be overexpressed in breast [40,59] endometrial [60,61], ovarian [62] and thyroid cancers [63]. The results presented here extend these observations to show that different types of lung cancers including adenocarcinomas, squamous cell carcinoma and large cell carcinomas express higher GPER than normal lung tissue.…”

Section: Discussionsupporting

confidence: 77%

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

et al. 2012

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BackgroundG-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.MethodsThe 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.ResultsAnalysis 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.ConclusionThe 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.

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“…186 Importantly, in patients treated only with tamoxifen, GPER protein expression increased and survival was significantly lower in patients with initial GPER-positive tumors, suggesting breast cancer patients with high GPER expression should not be treated with tamoxifen alone. {Ignatov, 2011 #2254} In addition, GPER is widely expressed in cancer cell lines and primary tumors of the breast, 17,18,34,177,184–188 endometrium, 178–180,189,190 ovaries, 47,53,181,191,192 thyroid, 180 lung, 182 prostate, 183 testicular germ cells 193 and the brain (unpublished work). In cell lines of thyroid, ovarian, endometrial and breast cancers, stimulation of GPER with 17β-estradiol 53,180,194 or other estrogenic compounds, such as atrazine, 47 genistein, 180 bisphenol A 46,195 or tamoxifen 194 activates a signaling mechanism that typically promotes proliferation, although inhibition of proliferation has also been reported.…”

Section: Gper In Physiology and Diseasementioning

confidence: 98%

“…184,186,188 Nevertheless, in general, GPER expression in breast cancers correlates with clinical and pathological biomarkers of poor outcome. High levels of GPER protein expression in samples of human breast cancers also correlate with increased tumor size and metastasis.…”

Section: Gper In Physiology and Diseasementioning

confidence: 99%

The G-protein-coupled estrogen receptor GPER in health and disease

2011

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Estrogens mediate profound effects throughout the body, and regulate physiological and pathological processes in both women and men. The decreased incidence of many diseases in premenopausal women is attributed to the presence of 17β-estradiol, the predominant and most potent endogenous estrogen. In addition to endogenous estrogens, however, several manmade and plant-derived molecules also exhibit estrogenic activity. Traditionally, the actions of 17β-estradiol are ascribed to two nuclear estrogen receptors (ERs), ERα and ERβ, which function as ligand-activated transcription factors. However, 17β-estradiol also mediates rapid signaling events via pathways that involve transmembrane ERs, such as G-protein-coupled ER 1, (GPER, formerly known as GPR30). In the past 10 years, GPER has been implicated in both rapid signaling and transcriptional regulation. With the discovery of GPER-selective ligands that can selectively modulate GPER function in cell experiments and preclinical studies, and the use of GPER-knockout mice, many more potential roles for GPER are currently being elucidated. This Review highlights the physiological roles of GPER in the reproductive, nervous, endocrine, immune and cardiovascular systems, as well as its pathological roles in a diverse array of disorders including cancer. GPER is emerging as a novel therapeutic target and prognostic indicator for these diseases.

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The Correlation between GPR30 and Clinicopathologic Variables in Breast Carcinomas

Cited by 14 publications

References 16 publications

G-protein Coupled Estrogen Receptor 1 Expression in Primary Breast Cancers and Its Correlation with Clinicopathological Variables

G-protein Coupled Estrogen Receptor 1 Expression in Primary Breast Cancers and Its Correlation with Clinicopathological Variables

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

The G-protein-coupled estrogen receptor GPER in health and disease

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