Brembeck, Felix H.

[["dc.bibliographiccitation.journal","Frontiers in Pediatrics"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Ragab, Nada"],["dc.contributor.author","Viehweger, Florian"],["dc.contributor.author","Bauer, Julia"],["dc.contributor.author","Geyer, Natalie"],["dc.contributor.author","Yang, Mingya"],["dc.contributor.author","Seils, Anna"],["dc.contributor.author","Belharazem, Djeda"],["dc.contributor.author","Brembeck, Felix H."],["dc.contributor.author","Schildhaus, Hans-Ulrich"],["dc.contributor.author","Marx, Alexander"],["dc.contributor.author","Hahn, Heidi"],["dc.contributor.author","Simon-Keller, Katja"],["dc.date.accessioned","2020-12-10T18:44:36Z"],["dc.date.available","2020-12-10T18:44:36Z"],["dc.date.issued","2018"],["dc.identifier.doi","10.3389/fped.2018.00378"],["dc.identifier.eissn","2296-2360"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/78522"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Canonical WNT/β-Catenin Signaling Plays a Subordinate Role in Rhabdomyosarcomas"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","6770"],["dc.bibliographiccitation.issue","16"],["dc.bibliographiccitation.journal","Oncotarget"],["dc.bibliographiccitation.lastpage","6787"],["dc.bibliographiccitation.volume","5"],["dc.contributor.author","Zatula, Nathalie"],["dc.contributor.author","Wiese, Maria"],["dc.contributor.author","Bunzendahl, Jens"],["dc.contributor.author","Birchmeier, Walter"],["dc.contributor.author","Perske, Christina"],["dc.contributor.author","Bleckmann, Annalen"],["dc.contributor.author","Brembeck, Felix H."],["dc.date.accessioned","2019-07-09T11:42:11Z"],["dc.date.available","2019-07-09T11:42:11Z"],["dc.date.issued","2014-08-30"],["dc.description.abstract","The majority of human breast cancers express estrogen receptor alpha (ER), which is important for therapy with anti-estrogens. Here we describe the role of BCL9-2, a proto-oncogene previously characterized as co-activator of Wnt/ß-catenin signaling, for mammary tumorigenesis in mice and human. ER positive human breast cancers showed overexpression of BCL9-2 and tamoxifen treated patients with high BCL9-2 demonstrated a better survival. BCL9-2 was upregulated during puberty and pregnancy in normal mammary epithelia, but downregulated in the involuted gland. BCL9-2 overexpression in vivo delayed the mammary involution and induced alveolar hyperplasia. Moreover, aged BCL9-2 transgenic mice developed ductal-like mammary tumors with high nuclear ER expression. We found, that primary cell cultures of BCL9-2 breast tumors responded to tamoxifen treatment. Moreover, BCL9-2 regulated the expression of ER and the proliferation of human breast cancer cells independently of ß-catenin. Finally, we describe a novel mechanism, how BCL9-2 regulates ER transcription by interaction with Sp1 through the proximal ESR1 gene promoter. In summary, BCL9-2 induces ER positive breast cancers in vivo, regulates ER expression by a novel ß-catenin independent mechanism in breast cancer cells, and might predict the therapy response to tamoxifen treatment."],["dc.identifier.doi","10.18632/oncotarget.2252"],["dc.identifier.pmid","25149534"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/12963"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/58610"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1949-2553"],["dc.rights","CC BY 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/3.0"],["dc.subject.mesh","Animals"],["dc.subject.mesh","Breast Neoplasms"],["dc.subject.mesh","Carcinogenesis"],["dc.subject.mesh","DNA-Binding Proteins"],["dc.subject.mesh","Estrogen Receptor alpha"],["dc.subject.mesh","Female"],["dc.subject.mesh","Humans"],["dc.subject.mesh","Mammary Neoplasms, Experimental"],["dc.subject.mesh","Mice"],["dc.subject.mesh","Mice, Transgenic"],["dc.subject.mesh","Tamoxifen"],["dc.subject.mesh","Transcription Factors"],["dc.subject.mesh","Transcriptional Activation"],["dc.subject.mesh","Wnt Signaling Pathway"],["dc.subject.mesh","beta Catenin"],["dc.title","The BCL9-2 proto-oncogene governs estrogen receptor alpha expression in breast tumorigenesis."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1359"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Gastroenterology"],["dc.bibliographiccitation.lastpage","U810"],["dc.bibliographiccitation.volume","141"],["dc.contributor.author","Brembeck, Felix H."],["dc.contributor.author","Wiese, Maria"],["dc.contributor.author","Zatula, Nathalie"],["dc.contributor.author","Grigoryan, Tamara"],["dc.contributor.author","Dai, Yiyang"],["dc.contributor.author","Fritzmann, Johannes"],["dc.contributor.author","Birchmeier, Walter"],["dc.date.accessioned","2018-11-07T08:51:06Z"],["dc.date.available","2018-11-07T08:51:06Z"],["dc.date.issued","2011"],["dc.description.abstract","BACKGROUND & AIMS: The roles of the 2 BCL9 and 2 Pygopus genes in Wnt to beta-catenin signaling are not clear in vertebrates. We examined their expression and function in normal and tumor intestinal epithelia in mice and humans. METHODS: Specific antibodies were generated to characterize the BCL9 and Pygopus proteins in normal intestine and in colon tumors. Targets of BCL9 and Pygopus in colon cancer cells were analyzed using small interfering RNA analysis. Transgenic mice were created that overexpressed BCL9-2 in intestine; these were crossed with APC(Min/+) mice to create BCL9-2; APC(Min/+) mice. RESULTS: BCL9 and Pygopus2 were expressed in all normal intestinal and colon cancer cells. BCL9-2 was detectable only in the villi, not in the crypts of normal intestine. BCL9-2 was up-regulated in adenomas and in almost all colon tumors, with a concomitant increase of Pygopus2, whereas levels of BCL9 were similar between normal and cancer cells. Transgenic overexpression of BCL9-2 in theintestine of BCL9-2; APC(Min/+) mice increased formation of adenomas that progressed to invasive tumors, resulting in reduced survival time. Using small interfering RNA analysis, we found that BCL9s and Pygopus are not targets of Wnt in colon cancer cells, but Wnt signaling correlated with levels of BCL9-2. BCL9-2 regulated expression of beta-catenin-dependent and -independent target genes that have been associated with early stages of intestinal tumorigenesis. CONCLUSIONS: BCL9-2 promotes early phases of intestinal tumor progression in humans and in transgenic mice. BCL9-2 increases the expression of a subset of canonical Wnt target genes but also regulates genes that are required for early stages of tumor progression."],["dc.identifier.doi","10.1053/j.gastro.2011.06.039"],["dc.identifier.isi","000295593700043"],["dc.identifier.pmid","21703997"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/21850"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","W B Saunders Co-elsevier Inc"],["dc.relation.issn","0016-5085"],["dc.title","BCL9-2 Promotes Early Stages of Intestinal Tumor Progression"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2739"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","Cancer Research"],["dc.bibliographiccitation.lastpage","2748"],["dc.bibliographiccitation.volume","70"],["dc.contributor.author","Nitzki, Frauke"],["dc.contributor.author","Zibat, Arne"],["dc.contributor.author","Koenig, Simone"],["dc.contributor.author","Wijgerde, Mark"],["dc.contributor.author","Rosenberger, Albert"],["dc.contributor.author","Brembeck, Felix H."],["dc.contributor.author","Carstens, Per-Ole"],["dc.contributor.author","Frommhold, Anke"],["dc.contributor.author","Uhmann, Anja"],["dc.contributor.author","Klingler, Stefan"],["dc.contributor.author","Reifenberger, Julia"],["dc.contributor.author","Pukrop, Tobias"],["dc.contributor.author","Aberger, Fritz"],["dc.contributor.author","Schulz-Schaeffer, Walter J."],["dc.contributor.author","Hahn, Heidi"],["dc.date.accessioned","2018-11-07T08:44:23Z"],["dc.date.available","2018-11-07T08:44:23Z"],["dc.date.issued","2010"],["dc.description.abstract","Basal cell carcinoma (BCC) is the most common skin tumor in humans. Although BCCs rarely metastasize, they can cause significant morbidity due to local aggressiveness. Approximately 20% of BCCs show signs of spontaneous regression. The understanding of molecular events mediating spontaneous regression has the potential to reduce morbidity of BCC and, potentially, other tumors, if translated into tumor therapies. We show that BCCs induced in conditional Ptch(flox/flox)ERT(2+/-) knockout mice regress with time and show a more differentiated phenotype. Differentiation is accompanied by Wnt5a expression in the tumor stroma, which is first detectable at the fully developed tumor stage. Coculture experiments revealed that Wnt5a is upregulated in tumor-adjacent macrophages by soluble signals derived from BCC cells. In turn, Wnt5a induces the expression of the differentiation marker K10 in tumor cells, which is mediated by Wnt/Ca(2+) signaling in a CaMKII-dependent manner. These data support a role of stromal Wnt5a in BCC differentiation and regression, which may have important implications for development of new treatment strategies for this tumor. Taken together, our results establish BCC as an easily accessible model of tumor regression. The regression of BCC despite sustained Hedgehog signaling activity seems to be mediated by tumor-stromal interactions via Wnt5a signaling. Cancer Res; 70(7); 2739-48. (C) 2010 AACR."],["dc.identifier.doi","10.1158/0008-5472.CAN-09-3743"],["dc.identifier.isi","000278486000019"],["dc.identifier.pmid","20233865"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/20187"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Assoc Cancer Research"],["dc.relation.issn","0008-5472"],["dc.title","Tumor Stroma-Derived Wnt5a Induces Differentiation of Basal Cell Carcinoma of Ptch-Mutant Mice via CaMKII"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","80612"],["dc.bibliographiccitation.issue","49"],["dc.bibliographiccitation.journal","Oncotarget"],["dc.bibliographiccitation.lastpage","80632"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Talla, Suranand B."],["dc.contributor.author","Brembeck, Felix H."],["dc.date.accessioned","2018-11-07T10:04:37Z"],["dc.date.available","2018-11-07T10:04:37Z"],["dc.date.issued","2016"],["dc.description.abstract","Pygo2 acts as a co-activator of Wnt signaling in a nuclear complex with beta-catenin/BCL9/BCL9-2 to increase target gene transcription. Previous studies showed that Pygo2 is upregulated in murine intestinal tumors and human colon cancer, but is apparently dispensable for normal intestinal homeostasis. Here, we have evaluated the in vivo role of Pygo2 during intestinal tumorigenesis using Pygo2 deficient mice. We analyzed chemically induced colon tumor development and conditional intestine specific mouse models harboring either Apc loss-of-function (LOF) or Ctnnb1 gain-of-function (beta-catenin GOF). Remarkably, the number and size of chemically induced tumors was significantly reduced in Pygo2 deficient mice, suggesting that Pygo2 has a tumor promoting function. Furthermore, loss of Pygo2 rescued early tumorigenesis of Ctnnb1 GOF mutants. In contrast, Pygo2 ablation was not sufficient to prevent tumor development of Apc LOF mice. The effect on tumor formation by Pygo2 knockout was linked to the repression of specific deregulated Wnt target genes, in particular of c-Myc. Moreover, the role of Pygo2 appears to be associated with the signaling output of deregulated Wnt signaling in the different tumor models. Thus, targeting Pygo2 might provide a novel strategy to suppress tumor formation in a context dependent manner."],["dc.description.sponsorship","Wilhelm Sander Stiftung [2011.093.1]"],["dc.identifier.doi","10.18632/oncotarget.13016"],["dc.identifier.isi","000389877500045"],["dc.identifier.pmid","27811361"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/38734"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Impact Journals Llc"],["dc.relation.issn","1949-2553"],["dc.title","The role of Pygo2 for Wnt/beta-catenin signaling activity during intestinal tumor initiation and progression"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]