Distribution of GPR30, a Seven Membrane–Spanning Estrogen Receptor, in Primary Breast Cancer and its Association with Clinicopathologic Determinants of Tumor Progression

Filardo, Edward J.; Graeber, C. T.; Quinn, Jeffrey A.; Resnick, Murray B.; Giri, Dilip; DeLellis, Ronald A.; Steinhoff, Margaret M.; Sabo, Edmond

doi:10.1158/1078-0432.ccr-06-0860

Cited by 322 publications

(347 citation statements)

References 45 publications

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“…GPER protein is expressed in ~50% of all breast cancers, regardless of their ER status [34]. Our studies reinforced that GPER was positive in 68.9% of our primary breast cancer specimens, although the number of the tissue samples was limited, the results still could indicate the wide distribution for GPER in breast cancers.…”

Section: Discussionsupporting

confidence: 73%

G Protein-Coupled Estrogen Receptor Is a Critical Regulator in Metastasis of Breast Cancer Cells

Gao¹,

Chen²,

Jiang³

2017

JBM

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Estrogen signaling via GPER in breast cancers has been intensively discussed over years, but the underlying molecular mechanism remains to be fully elucidated, especially for the transcriptional profiles of the GPER under estrogen stimulation. In this study, we evaluated the potential role GPER in regulating invasion of metastatic breast cancer cell line MDA-MB-231 via transcriptional way. First, with primary breast cancer tissue samples, we found that the expression of GPER significantly coordinated with another membrane receptor-CXCR1. Besides, the expression level of these two proteins was associated with the development of the primary breast cancers. Second, to dissect the cross talk between GPER and CXCR1, we further our studies to detect the activation of ERK, Akt and transcriptional factor NF-kB. We found that upon estrogen stimulation, the phosphorylation level of ERK and Akt were rapidly increased and then resulted in the activation and nucleus translocation of NF-kB. When we considered the sub-sequence of the NF-kB activation, we found the autocrine of IL-8 was boosted by stimulation of the estrogen and followed by the promoted invasion of the MDA-MB-231 cells. In conclusion, our data demonstrated the estrogen-mediated GPER stimulation would regulate the invasive activities of metastatic breast cancer cell line MDA-MB-231 coupled with another membrane receptor CXCR1 via transcriptional pathway, the cross talk between GPER and CXCR1 may be another target for breast cancer therapies.

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Section: Discussionsupporting

confidence: 73%

G Protein-Coupled Estrogen Receptor Is a Critical Regulator in Metastasis of Breast Cancer Cells

Gao¹,

Chen²,

Jiang³

2017

JBM

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“…These results indicate that PGRMC1 is probably involved in regulating GPER-dependent estrogen functions mediated through transactivation of EGFR in other tissues. GPER is expressed in a broad range of malignancies, including breast, ovarian, endometrial, prostate, and testicular cancers, as well as in tumors of non-reproductive tissues (Filardo et al 2006, Lappano et al 2013, and mediates estrogen actions such as cell growth through EGFR-dependent signaling in cancer cells (Filardo et al 2000. Collectively, results from these recent studies have implicated GPER in estrogen-dependent tumor progression through cross-talk with growth-factor signaling pathways, particularly EGFR (Lappano et al 2013).…”

Section: Discussionmentioning

confidence: 99%

Role of Pgrmc1 in estrogen maintenance of meiotic arrest in zebrafish oocytes through Gper/Egfr

Aizen¹,

Thomas²

2015

Journal of Endocrinology

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The regulation of receptor trafficking to the cell surface and its effect on responses of target cells to growth factors and hormones remain poorly understood. Initial evidence has been recently obtained using cancer cells that surface expression of the epidermal growth factor receptor (EGFR) is dependent on its association with progesterone receptor membrane component 1 (PGRMC1). Estrogen inhibition of oocyte maturation (OM) in zebrafish is mediated through G-protein-coupled estrogen membrane receptor 1 (Gper1) and involves activation of Egfr. Therefore, in this study, the potential roles of Pgrmc1 in the cell surface expression and functions of Egfr in normal cells were investigated in this in vitro OM model of Egfr action using an inhibitor of PGMRC1 signaling, AG205. A single w60 kDa protein band, which corresponds to the size of the Pgrmc1 dimer, was detected on plasma membranes of fully grown oocytes by western blotting. Co-treatment with the PGRMC1 inhibitor AG205 (20 mM) blocked the inhibitory effects of 100 nM estradiol-17b and the GPER agonist, G-1, on spontaneous maturation of denuded zebrafish oocytes. Moreover, reversal of these estrogen effects on OM by the EGFR inhibitors AG1478 and AG825 (50 mM) was prevented by co-incubation with the PGRMC1 inhibitor. Inhibition of Pgrmc1 signaling with AG205 also caused a decrease in Egfr-dependent signaling and Egfr expression on oocyte cell membranes. These results indicate that maintenance of Pgrmc1 signaling is required for Egfr expression on zebrafish oocyte cell membranes and for conserving the functions of Egfr in maintaining meiotic arrest through estrogen activation of Gper.

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“…Surprisingly, a member of the GPCR family, GPR30/GPER, was recently shown to mediate the multifaceted actions of estrogens in different tissues including cancer cells [135] . Importantly, GPER overexpression was associated with lower survival rates in endometrial and ovarian cancer patients and with an elevated risk of developing metastases in patients with breast cancer [136][137][138] . GPER by transactivating EGFR triggers numerous transduction pathways including the intracellular cAMP, calcium mobilization, MAPK, PI3-K and phospholipase C activation in a variety of cell types [139] .…”

Section: Gpcrs Activated By Hormonesmentioning

confidence: 99%

GPCRs and cancer

Lappano

2012

Acta Pharmacol Sin

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G-protein-coupled receptors (GPCRs), which represent the largest gene family in the human genome, play a crucial role in multiple physiological functions as well as in tumor growth and metastasis. For instance, various molecules like hormones, lipids, peptides and neurotransmitters exert their biological effects by binding to these seven-transmembrane receptors coupled to heterotrimeric G-proteins, which are highly specialized transducers able to modulate diverse signaling pathways. Furthermore, numerous responses mediated by GPCRs are not dependent on a single biochemical route, but result from the integration of an intricate network of transduction cascades involved in many physiological activities and tumor development. This review highlights the emerging information on the various responses mediated by a selected choice of GPCRs and the molecular mechanisms by which these receptors exert a primary action in cancer progression. These findings provide a broad overview on the biological activity elicited by GPCRs in tumor cells and contribute to the identification of novel pharmacological approaches for cancer patients.

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Distribution of GPR30, a Seven Membrane–Spanning Estrogen Receptor, in Primary Breast Cancer and its Association with Clinicopathologic Determinants of Tumor Progression

Cited by 322 publications

References 45 publications

G Protein-Coupled Estrogen Receptor Is a Critical Regulator in Metastasis of Breast Cancer Cells

G Protein-Coupled Estrogen Receptor Is a Critical Regulator in Metastasis of Breast Cancer Cells

Role of Pgrmc1 in estrogen maintenance of meiotic arrest in zebrafish oocytes through Gper/Egfr

GPCRs and cancer

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