Girgert, Rainer

[["dc.bibliographiccitation.firstpage","199"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Breast Cancer Research and Treatment"],["dc.bibliographiccitation.lastpage","205"],["dc.bibliographiccitation.volume","134"],["dc.contributor.author","Girgert, Rainer"],["dc.contributor.author","Emons, Guenter"],["dc.contributor.author","Gruendker, Carsten"],["dc.date.accessioned","2018-11-07T09:08:33Z"],["dc.date.available","2018-11-07T09:08:33Z"],["dc.date.issued","2012"],["dc.description.abstract","Triple-negative breast cancers lack estrogen receptor alpha (ER alpha), progesterone receptor, and do not overexpress human epidermal growth factor receptor 2 (Her-2). They are neither susceptible to endocrine therapy nor to a therapy using the anti-Her-2 antibody, trastuzumab. Therefore, an efficient targeted therapy is warranted. Triple-negative breast tumors frequently express membrane bound estrogen receptor G-protein coupled receptor (GPR30). As proof of principle, we analyzed the consequences of a knock-down of GPR30 expression on the growth regulation of triple-negative breast cancer cell lines. Cells of triple-negative breast cancer cell lines were transfected with siRNA against GPR30 or control siRNA, and cell growth was stimulated either with 10(-9) M 17 beta-estradiol or 10(-6) M 4-hydroxytamoxifen. Cell proliferation was measured using Alamar blue staining. Activation of c-Src and epidermal growth factor (EGF)-receptor was assessed using western blot. Expression of c-fos was quantified by reverse transcription polymerase chain reaction. Seven days after transfection with siRNA, GPR30 mRNA in triple-negative breast cancer cell lines MDA-MB-435 and HCC1806 was reduced by 74 and 90%, respectively. 10(-8) M 17 beta-estradiol enhanced proliferation of MDA-MB-435 to 129.6 +/- A 5.4% of control (p < 0.05) and HCC1806 to 156.9 +/- A 15.4% of control (p < 0.05), respectively. 10(-6) M 4-hydroxytamoxifen increased cell number of MDA-MB-435 to 121.0 +/- A 6.9% of control (p < 0.05) and HCC1806 to 124.5 +/- A 12.1% of control (n.s.), respectively. This increased proliferation by the two estrogenic compounds was completely prevented by knock-down of GPR30 expression in both cell lines. In control cells, activity of Src kinase was increased 3-fold by estradiol and 3.8-fold using 4-hydroxytamoxifen. Transactivation of the EGF-receptor was similarly increased in both cell lines by 17 beta-estradiol and 4-hydroxytamoxifen. Both compounds increased c-fos expression 1.5- and 3.1-fold, respectively. Knock-down of GPR30 expression completely abolished activation of all these signaling pathways responsible for enhanced proliferation. A pharmacological inhibition of GPR30 by specific small molecular inhibitors might prove to be an appropriate targeted therapy of triple-negative breast cancer in the future."],["dc.identifier.doi","10.1007/s10549-012-1968-x"],["dc.identifier.isi","000306437500018"],["dc.identifier.pmid","22290080"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/8116"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/26060"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.issn","0167-6806"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Inactivation of GPR30 reduces growth of triple-negative breast cancer cells: possible application in targeted therapy"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","19"],["dc.bibliographiccitation.journal","Fibrogenesis & Tissue Repair"],["dc.bibliographiccitation.lastpage","10"],["dc.bibliographiccitation.volume","3"],["dc.contributor.author","Girgert, Rainer"],["dc.contributor.author","Martin, Maria"],["dc.contributor.author","Kruegel, Jenny"],["dc.contributor.author","Miosge, Nicolai"],["dc.contributor.author","Temme, Johanna"],["dc.contributor.author","Eckes, Beate"],["dc.contributor.author","Müller, Gerhard-Anton"],["dc.contributor.author","Gross, Oliver"],["dc.date.accessioned","2019-07-09T11:52:48Z"],["dc.date.available","2019-07-09T11:52:48Z"],["dc.date.issued","2010"],["dc.description.abstract","Background: Integrins are important cellular receptors for collagens. Within the glomerulus, podocytes regulate the integrity of the glomerular basement membrane (GBM) by sensing the presence of collagen and regulating collagen IV synthesis. The present study evaluates the role of integrin a2 (ITGA2) in cell-matrix interaction. Methods and Results: ITGA2-deficient mice had normal renal function but moderate proteinuria and enhanced glomerular and tubulointerstitial matrix deposition. Electron microscopy demonstrated irregular podocyte-matrix interaction, causing pathological protrusions towards the urinary (podocyte) side of the GBM. These characteristic subepithelial bulges mimic the renal phenotype of mice, which are deficient in another collagen receptor, discoidin domain receptor (DDR)1. Using immunogold staining, ITGA2 expression was found to localize to the basolateral site of the podocyte foot processes. ITGA2-deficient mice overexpressed transforming growth factor (TGF)b and connective tissue growth factor (CTGF) compared with wild-type mice. Using in situ hybridization, tubular cells were found to be the primary site of TGFb synthesis and podocytes the source of CTGF in ITGA2- deficient mice. Conclusion: These findings support our hypothesis that both these collagen receptors (ITGA2 and DDR1) play a similar role within the kidney. Further, cell-matrix interaction via collagen receptors seems to be crucial for maintenance of normal GBM architecture and function. Targeting collagen receptors such as ITGA2 might be a new form of treatment for progressive fibrotic diseases."],["dc.identifier.doi","10.1186/1755-1536-3-19"],["dc.identifier.fs","575629"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6018"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/60281"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.intern","In goescholar not merged with http://resolver.sub.uni-goettingen.de/purl?gs-1/6905 but duplicate"],["dc.rights","Goescholar"],["dc.rights.access","openAccess"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.subject.ddc","610"],["dc.title","Integrin a2-deficient mice provide insights into specific functions of collagen receptors in the kidney"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2958"],["dc.bibliographiccitation.issue","13"],["dc.bibliographiccitation.journal","Journal of Clinical Medicine"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Rubel, Diana"],["dc.contributor.author","Zhang, Yanqin"],["dc.contributor.author","Sowa, Nenja"],["dc.contributor.author","Girgert, Rainer"],["dc.contributor.author","Gross, Oliver"],["dc.date.accessioned","2021-08-12T07:46:00Z"],["dc.date.available","2021-08-12T07:46:00Z"],["dc.date.issued","2021"],["dc.description.abstract","Angiotensin-converting enzyme inhibitors (ACEi) delay progression of the inherited renal disease Alport syndrome. However, the effect of ACEis weakens gradually due to an “aldosterone escape”. Here, we investigate if an aldosterone antagonist can counteract loss of ACEi-efficacy. COL4A3-/- mice were treated with ramipril (ACEi), starting at 4.5 weeks of age, and spironolactone was added at 7 weeks of age. Lifespan until renal failure, as well as kidney function parameters, were investigated. Dual therapy decreased proteinuria levels compared to ACEi monotherapy. Matrix accumulation, as well as tubulointerstitial and glomerular scar-tissue formation, were significantly reduced compared to untreated mice and ACEi-monotherapy at 75 and 100 days. Lifespan in dual treated mice was extended compared to untreated mice. However, lifespan was not superior to ACEi monotherapy–despite improved urea-nitrogen levels in the dual therapy group. In conclusion, adding the aldosterone-antagonist spironolactone to ACEi therapy further improved kidney function and reduced proteinuria and fibrosis. However, survival was not improved further, possibly due to premature death from side effects of dual therapy such as hyperkalemia. Thus, dual therapy could offer an effective therapy option for Alport syndrome patients with progressive proteinuria. However, the risks of adverse events require close monitoring."],["dc.description.abstract","Angiotensin-converting enzyme inhibitors (ACEi) delay progression of the inherited renal disease Alport syndrome. However, the effect of ACEis weakens gradually due to an “aldosterone escape”. Here, we investigate if an aldosterone antagonist can counteract loss of ACEi-efficacy. COL4A3-/- mice were treated with ramipril (ACEi), starting at 4.5 weeks of age, and spironolactone was added at 7 weeks of age. Lifespan until renal failure, as well as kidney function parameters, were investigated. Dual therapy decreased proteinuria levels compared to ACEi monotherapy. Matrix accumulation, as well as tubulointerstitial and glomerular scar-tissue formation, were significantly reduced compared to untreated mice and ACEi-monotherapy at 75 and 100 days. Lifespan in dual treated mice was extended compared to untreated mice. However, lifespan was not superior to ACEi monotherapy–despite improved urea-nitrogen levels in the dual therapy group. In conclusion, adding the aldosterone-antagonist spironolactone to ACEi therapy further improved kidney function and reduced proteinuria and fibrosis. However, survival was not improved further, possibly due to premature death from side effects of dual therapy such as hyperkalemia. Thus, dual therapy could offer an effective therapy option for Alport syndrome patients with progressive proteinuria. However, the risks of adverse events require close monitoring."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft"],["dc.description.sponsorship","K. C. Wong Education Foundation"],["dc.description.sponsorship","Deutscher Akademischer Austauschdienst"],["dc.identifier.doi","10.3390/jcm10132958"],["dc.identifier.pii","jcm10132958"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/88593"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-448"],["dc.publisher","MDPI"],["dc.relation.eissn","2077-0383"],["dc.rights","https://creativecommons.org/licenses/by/4.0/"],["dc.title","Organoprotective Effects of Spironolactone on Top of Ramipril Therapy in a Mouse Model for Alport Syndrome"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","781"],["dc.bibliographiccitation.journal","Frontiers in Endocrinology"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Girgert, Rainer"],["dc.contributor.author","Emons, Günter"],["dc.contributor.author","Gründker, Carsten"],["dc.date.accessioned","2019-07-09T11:49:51Z"],["dc.date.available","2019-07-09T11:49:51Z"],["dc.date.issued","2019"],["dc.description.abstract","Estrogen receptors are important regulators of the growth of breast tumors. Three different receptors for estrogens have been identified in breast tumors, two nuclear receptors, ERa and ERb, and a G-protein coupled estrogen receptor 1 (GPER) that initiates non-genomic effects of estrogens in the cytosol. Recent findings show that the stimulation of cytoplasmic ERa and ERb also triggers non-genomic signaling pathways. The treatment of breast cancer with anti-estrogens depends on the presence of ERa. About 40% of all breast cancers, however, do not express ERa. One subgroup of these tumors overexpress Her-2, another important group is designated as triple-negative breast cancer, as they neither express ERa, nor progesterone receptors, nor do they overexpress Her-2. This review addresses the signaling of ERb and GPER in ERa-negative breast tumors. In addition to the well-established EGF-receptor transactivation pathways of GPER, more recent findings of GPER-dependent activation of FOXO3a, the Hippo-pathway, and HOTAIR-activation are summarized."],["dc.identifier.doi","10.3389/fendo.2018.00781"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15794"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59644"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.publisher","Frontiers Media S.A."],["dc.relation.eissn","1664-2392"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","Estrogen Signaling in ERα-Negative Breast Cancer: ERβ and GPER"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","935"],["dc.bibliographiccitation.journal","BMC Cancer"],["dc.bibliographiccitation.volume","14"],["dc.contributor.author","Girgert, Rainer"],["dc.contributor.author","Emons, Guenter"],["dc.contributor.author","Gruendker, Carsten"],["dc.date.accessioned","2018-11-07T09:31:19Z"],["dc.date.available","2018-11-07T09:31:19Z"],["dc.date.issued","2014"],["dc.description.abstract","Background: Due to the lack of ER alpha, triple negative breast cancers (TNBCs) are not susceptible to endocrine therapy using antiestrogens. However, the majority of TNBCs express the membrane bound estrogen receptor GPR30. We have recently shown that knock-down of GPR30 expression prevented growth stimulation of TNBC cell lines by 17 beta-estradiol. Now we analyzed whether specific inhibition of GPR30 represents a new option for therapy of TNBC. Methods: Growth of TNBC cells was assessed using Alamar-blue colorimetric assay. Activation of c-Src and EGF-receptor was assessed using Western blots. Expression of c-fos, cyclin D1 and aromatase was quantified by RT-PCR. G alpha-specific signaling of GPR30 was analyzed by electrophoretic mobility shift assay. Results: HCC1806 cells showed the highest GPR30 expression, in HCC70 cells it was clearly lower, in MDA-MB-231 cells it was lowest. 10(-8) M 17 beta-estradiol significantly increased proliferation of HCC1806 cells to 134 +/- 12% of control (p < 0.01). Proliferation of HCC70 cells was slightly increased to 116 +/- 8% of control. Estriol significantly reduced cell number of HCC1806 cells to 16 c 12% (p < 0.01). Cell number of HCC70 cells and of MDA-MB-231 cells was reduced to 68 +/- 25% and to 61 +/- 10%, respectively. Activity of Src kinase increased to 150 +/- 10% (p < 0.05) by 10(-8) M 17 beta-estradiol treatment in HCC1806 and to 220 +/- 20% in HCC70 cells (p < 0.01). Estriol treatment completely inhibited 17 beta-estradiol-induced p-src activation. Transactivation of EGF-receptor increased by estradiol treatment to 350% in HCC1806 and to 280% in HCC70 cells. Estriol completely suppressed EGF-receptor transactivation. c-fos expression increased to 260% and to 190%, respectively. Estriol reduced this induction to 160% (HCC1806) and below control in HCC70 cells. Cyclin D1 was induced to 290% (HCC1806) and 170% (HCC70) and completely inhibited by estriol. 17 beta-estradiol increased CREB-phosphorylation to 400%. Binding of phospho-CREB to a CRE of cyclin D1 was enhanced to 320%. Conclusion: Specific pharmacological inhibition of GPR30 might become a promising targeted therapy for TNBC in future."],["dc.description.sponsorship","German Research Foundation [GR 1895/10-1]"],["dc.identifier.doi","10.1186/1471-2407-14-935"],["dc.identifier.isi","000347961900001"],["dc.identifier.pmid","25496649"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/11417"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/31514"],["dc.notes.intern","Merged from goescholar"],["dc.notes.intern","In goescholar not merged with http://resolver.sub.uni-goettingen.de/purl?gs-1/12301 but duplicate"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Biomed Central Ltd"],["dc.relation.issn","1471-2407"],["dc.rights","CC BY 4.0"],["dc.rights.access","openAccess"],["dc.rights.holder","Rainer Girgert et al.; licensee BioMed Central Ltd."],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Inhibition of GPR30 by estriol prevents growth stimulation of triple-negative breast cancer cells by 17 beta-estradiol"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","23"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Journal of Pineal Research"],["dc.bibliographiccitation.lastpage","31"],["dc.bibliographiccitation.volume","47"],["dc.contributor.author","Girgert, Rainer"],["dc.contributor.author","Hanf, Volker"],["dc.contributor.author","Emons, Guenter"],["dc.contributor.author","Gruendker, Carsten"],["dc.date.accessioned","2018-11-07T08:27:21Z"],["dc.date.available","2018-11-07T08:27:21Z"],["dc.date.issued","2009"],["dc.description.abstract","Melatonin possesses anti-estrogenic effects on estrogen receptor expressing (ER+) breast cancer cells in culture by reducing cell cycle progression and cell proliferation. There is increasing agreement that on a cellular level the effects of melatonin are primarily induced by the membrane-bound receptor MT1. The participation of a second, nuclear receptor of the group of ligand-dependent transcription factors, called RZR alpha, is under debate. In this study we used a number of breast cancer cell lines differing in their expression of the estrogen receptor and the two known melatonin receptors. In MCF-7 breast cancer cells transfected with a vector carrying the MT1 gene (MCF-7Mel1a) binding of CREB-protein to the cAMP-responsive element of the breast cancer suppressing gene BRCA-1 was more strongly reduced by treatment with melatonin than in the parental cells. Expression of estrogen responsive genes was determined in serum-starved cells, cells stimulated for 16 hr with estradiol and cells subsequently treated with melatonin. Expression of BRCA-1, p53, p21(WAF) and c-myc were up-regulated by estradiol. Treatment of the stimulated cells with melatonin counteracted the increase induced by estradiol almost completely. The more MT1 a cell line expressed, the stronger was the reduction of the expression of the estradiol-induced genes. There was no correlation between the expression of the nuclear receptor RZR alpha and the effects of melatonin on these genes."],["dc.identifier.doi","10.1111/j.1600-079X.2009.00684.x"],["dc.identifier.isi","000267706300004"],["dc.identifier.pmid","19522736"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6112"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/16188"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell Publishing, Inc"],["dc.relation.issn","0742-3098"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Membrane-bound melatonin receptor MT1 down-regulates estrogen responsive genes in breast cancer cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]