Disease relevance of GPR30

• Our data imply that ER-negative breast tumors that continue to express GPR30 may use estrogen to drive growth factor-dependent cellular responses [1].
• We stably introduced GPR30 in immortalized normal mammary epithelial (HME) cells using retroviruses for gene delivery [2].
• The LERGU mRNA was also detected in eight gastric cancer cell lines, but GPR30 mRNA scarcely existed [3].
• Transfecting a GPR30 antisense expression vector in both endometrial cancer cell lines, OHT was no longer able to induce growth effects, whereas the proliferative response to E2 was completely abrogated only in HEC1A cells [4].
• In addition, GPR30 showed a positive association with metastasis (P = 0.014; odds ratio, 1.9) [5].

High impact information on GPR30

• We found that suppression of GPR30 but not ER-alpha prevented E2-BSA- or E2-induced PKA activation and Bcl-2 expression [6].
• At 2 hours after trauma-hemorrhage, administration of E2-conjugated to bovine serum albumin (E2-BSA, membrane impermeable) or E2 induced the up-regulation of ER-alpha and GPR30 and attenuated hepatic injury [6].
• Isolated hepatocytes were transfected with small interfering RNA to suppress GPR30 or ER [6].
• GPR30 also acts independently of the ER to promote activation of the protein kinase A (PKA) pathway, which protects cells from apoptosis through Bcl-2 [6].
• G protein-coupled receptor 30-dependent protein kinase a pathway is critical in nongenomic effects of estrogen in attenuating liver injury after trauma-hemorrhage [6].

Chemical compound and disease context of GPR30

• Here, the significance of GPR30 in human breast cancer was evaluated by comparing its relationship to steroid hormone receptor expression and tumor progression variables [5].
• Additionally, GPR30 upregulation by progestin correlated with growth inhibition when a comparison was made between different breast cancer cell lines [7].
• A transcript of G-protein-coupled receptor 30 (GPR30) was upregulated by MPA in estrogen-treated MCF-7 breast cancer cells [7].

Biological context of GPR30

• Transfection of GPR30 into MDA-MB-231 cells restores their ability to stimulate adenylyl cyclase and attenuate EGF-induced activation of Erk-1/-2 by estrogen [8].
• Transfection of MDA-MB-231 cells with a GPR30 complementary DNA resulted in overexpression of GPR30 protein and conversion to an estrogen-responsive phenotype [1].
• Epidermal growth factor receptor (EGFR) transactivation by estrogen via the G-protein-coupled receptor, GPR30: a novel signaling pathway with potential significance for breast cancer [9].
• Transient expression of GPR30 resulted in a marked inhibition of cell proliferation independent of estrogen treatment [10].
• Coupled with our previous findings, the data imply that up-regulation of GPR30 by progestin leads to ERK-1 and -2 inactivation associated with MPA-induced growth inhibition [11].

Anatomical context of GPR30

• A high-affinity (dissociation constant 2.7 nm), limited capacity, displaceable, single binding site specific for estrogens was detected in plasma membranes of SKBR3 breast cancer cells that express GPR30 but lack nuclear estrogen receptors [12].
• Antisense oligonucleotide against guanine nucleotide-binding protein-coupled receptor, GPR30 suppressed the E2-induced cyclic adenosine monophosphate signal, c-Fos expression, and nerve growth factor secretion in both types of macrophages [13].
• Based upon PCR analysis in hybrid cell lines, the gene for GPCR-Br (HGMW-approved symbol GPR30) was mapped to chromosome 7p22 [14].
• We found that of all G protein-coupled receptors characterized to date, GPR30 is uniquely localized to the endoplasmic reticulum, where it specifically binds estrogen and fluorescent estrogen derivatives [15].
• These data indicate that GPR30, a transmembrane receptor for estrogen, is localized to the plasma membrane of CA2 pyramidal neuronal cells of the hippocampus in rat brain [16].

Associations of GPR30 with chemical compounds

• Thus, our data delineate a novel mechanism, requiring GPR30 and estrogen, that acts to regulate Erk-1/-2 activity via an inhibitory signal mediated by cAMP [8].
• In addition, GPR30-dependent Erk-1/-2 activation was triggered by ER antagonists, including ICI 182,780, yet not by 17alpha-estradiol or progesterone [1].
• These data suggest that the orphan receptor, GPR30, is important for the inhibitory effect of progestin on growth [10].
• Progesterone-induced increases and small interfering RNA-induced decreases in GPR30 expression in SKBR3 cells were accompanied by parallel changes in specific estradiol-17beta (E2) binding [12].
• Interestingly, the decrease of ERK activity induced by MPA was abrogated by GPR30 antisense [11].

Regulatory relationships of GPR30

• In this study, we investigate the role of GPR30 in regulating cell proliferation and mediating progestin-induced growth inhibition [10].
• Progestin and G protein-coupled receptor 30 inhibit mitogen-activated protein kinase activity in MCF-7 breast cancer cells [11].

Other interactions of GPR30

• MDA-MB-231 cells, which express ERbeta, but not ERalpha, and low levels of GPR30 protein, are unable to stimulate adenylyl cyclase or promote estrogen-mediated blockade of EGF-induced activation of Erk-1/-2 [8].
• Moreover, GPR30-dependent, cAMP-mediated attenuation of EGF-induced Erk-1/-2 activity was achieved by ER antagonists such as tamoxifen or ICI 182, 780; yet not by 17alpha-E2 or progesterone [8].
• Evidence is provided that attenuation of Erk-1/-2 activity by estrogen occurs via GPR30-dependent stimulation of adenylyl cyclase and cAMP-dependent signaling that results in Raf-1 inactivation [8].
• Here, evidence is provided that estrogen-induced Erk-1/-2 activation occurs independently of known estrogen receptors, but requires the expression of the G protein-coupled receptor homolog, GPR30 [1].
• Through fluorescence in situ hybridization analysis the gene encoding GPR30 was localized to chromosome 7p22 and GPR35 to chromosome 2q37.3 [17].
• These results suggest that GPR30-mediated inhibition of urothelial cell proliferation is the result of decreased cyclin D1 by down-regulation of activation protein-1 signaling [18].

Analytical, diagnostic and therapeutic context of GPR30

• We confirmed the existence of a novel mRNA in GPR30 3'UTR by northern blotting, cloned this novel mRNA and named it Leucine Rich Protein in GPR30 3'UTR (LERGU) [3].
• The images on transmission electron microscopy show that GPR30 is localized to a particular region associated with the plasma membranes of the pyramidal cells [16].
• The Civilian External Peer Review Program (CEPRP) of the Department of Defense health care system conducted a retrospective study of 5642 patients who underwent laparoscopic cholecystectomies at 89 military medical treatment facilities from July 1990 through May 1992 [19].
• They increased not only in the group using PIPC, CEZ, CEPR, CMZ, and LMOX by drip infusion but also in the group without prophylactic use of antibiotics [20].

References