Emons, Günter

[["dc.bibliographiccitation.artnumber","187"],["dc.bibliographiccitation.journal","Frontiers in Endocrinology"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Gründker, Carsten"],["dc.contributor.author","Emons, Günter"],["dc.date.accessioned","2019-07-09T11:43:36Z"],["dc.date.available","2019-07-09T11:43:36Z"],["dc.date.issued","2017"],["dc.description.abstract","In several human malignant tumors of the urogenital tract, including cancers of the endometrium, ovary, urinary bladder, and prostate, it has been possible to identify expression of gonadotropin-releasing hormone (GnRH) and its receptor as part of an autocrine system, which regulates cell proliferation. The expression of GnRH receptor has also been identified in breast cancers and non-reproductive cancers such as pancreatic cancers and glioblastoma. Various investigators have observed dose- and timedependent growth inhibitory effects of GnRH agonists in cell lines derived from these cancers. GnRH antagonists have also shown marked growth inhibitory effects on most cancer cell lines. This indicates that in the GnRH system in cancer cells, there may not be a dichotomy between GnRH agonists and antagonists. The well-known signaling mechanisms of the GnRH receptor, which are present in pituitary gonadotrophs, are not involved in forwarding the antiproliferative effects of GnRH analogs in cancer cells. Instead, the GnRH receptor activates a phosphotyrosine phosphatase (PTP) and counteracts with the mitogenic signal transduction of growth factor receptors, which results in a reduction of cancer cell proliferation. The PTP activation, which is induced by GnRH, also inhibits G-protein-coupled estrogen receptor 1 (GPER), which is a membrane- bound receptor for estrogens. GPER plays an important role in breast cancers, which do not express the estrogen receptor α (ERα). In metastatic breast, ovarian, and endometrial cancer cells, GnRH reduces cell invasion in vitro, metastasis in vivo, and the increased expression of S100A4 and CYR61. All of these factors play important roles in epithelial–mesenchymal transition. This review will summarize the present state of knowledge about the GnRH receptor and its signaling in human cancers."],["dc.identifier.doi","10.3389/fendo.2017.00187"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14591"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/58927"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.publisher","Frontiers Media S.A."],["dc.relation.eissn","1664-2392"],["dc.relation.issn","1664-2392"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","The Role of Gonadotropin-Releasing Hormone in Cancer Cell Proliferation and Metastasis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["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.firstpage","1387"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","Journal of Cancer Research and Clinical Oncology"],["dc.bibliographiccitation.lastpage","1391"],["dc.bibliographiccitation.volume","135"],["dc.contributor.author","Emons, Günter"],["dc.contributor.author","Kimmig, Rainer"],["dc.date.accessioned","2019-07-09T11:52:22Z"],["dc.date.available","2019-07-09T11:52:22Z"],["dc.date.issued","2009"],["dc.identifier.doi","10.1007/s00432-009-0581-9"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?goescholar/3538"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/60167"],["dc.notes.intern","Merged from goescholar"],["dc.publisher","Springer"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.subject.ddc","610"],["dc.title","Interdisciplinary S2k guidelines on the diagnosis and treatment of endometrial carcinoma"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","R49"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","BREAST CANCER RESEARCH"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Gruendker, Carsten"],["dc.contributor.author","Foest, Crispin"],["dc.contributor.author","Fister, Stefanie"],["dc.contributor.author","Nolte, Nadine"],["dc.contributor.author","Guenthert, Andreas R."],["dc.contributor.author","Emons, Guenter"],["dc.date.accessioned","2018-11-07T08:47:14Z"],["dc.date.available","2018-11-07T08:47:14Z"],["dc.date.issued","2010"],["dc.description.abstract","Introduction: Triple-negative breast cancer does not express estrogen and progesterone receptors, and no overexpression/amplification of the HER2-neu gene occurs. Therefore, this subtype of breast cancer lacks the benefits of specific therapies that target these receptors. Today chemotherapy is the only systematic therapy for patients with triple-negative breast cancer. About 50% to 64% of human breast cancers express receptors for gonadotropin-releasing hormone (GnRH), which might be used as a target. New targeted therapies are warranted. Recently, we showed that antagonists of gonadotropin-releasing hormone type II (GnRH-II) induce apoptosis in human endometrial and ovarian cancer cells in vitro and in vivo. This was mediated through activation of stress-induced mitogen-activated protein kinases (MAPKs) p38 and c-Jun N-terminal kinase (JNK), followed by activation of proapoptotic protein Bax, loss of mitochondrial membrane potential, and activation of caspase-3. In the present study, we analyzed whether GnRH-II antagonists induce apoptosis in MCF-7 and triple-negative MDA-MB-231 human breast cancer cells that express GnRH receptors. In addition, we ascertained whether knockdown of GnRH-I receptor expression affects GnRH-II antagonist-induced apoptosis and apoptotic signaling. Methods: Induction of apoptosis was analyzed by measurement of the loss of mitochondrial membrane potential. Apoptotic signaling was measured with quantification of activated MAPK p38 and caspase-3 by using the Western blot technique. GnRH-I receptor protein expression was inhibited by using the antisense knockdown technique. In vivo experiments were performed by using nude mice bearing xenografted human breast tumors. Results: We showed that treatment of MCF-7 and triple-negative MDA-MB-231 human breast cancer cells with a GnRH-II antagonist results in apoptotic cell death in vitro via activation of stress-activated MAPK p38 and loss of mitochondrial membrane potential. In addition, we showed GnRH-II antagonist-induced activation of caspase-3 in MDA-MB-231 human breast cancer cells. After knockdown of GnRH-I receptor expression, GnRH-II antagonist-induced apoptosis and apoptotic signaling was only slightly reduced, indicating that an additional pathway mediating the effects of GnRH-II antagonists may exist. The GnRH-I receptor seems not to be the only target of GnRH-II antagonists. The antitumor effects of the GnRH-II antagonist could be confirmed in nude mice. The GnRH-II antagonist inhibited the growth of xenotransplants of human breast cancers in nude mice completely, without any apparent side effects. Conclusions: GnRH-II antagonists seem to be suitable drugs for an efficacious and less-toxic endocrine therapy for breast cancers, including triple-negative breast cancers."],["dc.description.sponsorship","Deutsche Krebshilfe [106176, 107704]"],["dc.identifier.doi","10.1186/bcr2606"],["dc.identifier.isi","000285504100005"],["dc.identifier.pmid","20630060"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/5668"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/20899"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Biomed Central Ltd"],["dc.relation.issn","1465-5411"],["dc.rights","Goescholar"],["dc.rights.access","openAccess"],["dc.rights.holder","Grundker et al.; licensee BioMed Central Ltd."],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.subject.ddc","610"],["dc.title","Gonadotropin-releasing hormone type II antagonist induces apoptosis in MCF-7 and triple-negative MDA-MB-231 human breast cancer cells in vitro and in vivo"],["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"]]