Brembeck, Felix H.

[["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"]]