Bleckmann, Annalen

[["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","15482"],["dc.bibliographiccitation.issue","17"],["dc.bibliographiccitation.journal","Oncotarget"],["dc.bibliographiccitation.lastpage","15493"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Rietkötter, Eva"],["dc.contributor.author","Bleckmann, Annalen"],["dc.contributor.author","Bayerlová, Michaela"],["dc.contributor.author","Menck, Kerstin"],["dc.contributor.author","Chuang, Han-Ning"],["dc.contributor.author","Wenske, Britta"],["dc.contributor.author","Schwartz, Hila"],["dc.contributor.author","Erez, Neta"],["dc.contributor.author","Binder, Claudia"],["dc.contributor.author","Hanisch, Uwe-Karsten"],["dc.contributor.author","Pukrop, Tobias"],["dc.date.accessioned","2019-07-09T11:42:37Z"],["dc.date.available","2019-07-09T11:42:37Z"],["dc.date.issued","2015-06-20"],["dc.description.abstract","The mononuclear phagocytic system is categorized in three major groups: monocyte-derived cells (MCs), dendritic cells and resident macrophages. During breast cancer progression the colony stimulating factor 1 (CSF-1) can reprogram MCs into tumor-promoting macrophages in the primary tumor. However, the effect of CSF-1 during colonization of the brain parenchyma is largely unknown. Thus, we analyzed the outcome of anti-CSF-1 treatment on the resident macrophage population of the brain, the microglia, in comparison to MCs, alone and in different in vitro co-culture models. Our results underline the addiction of MCs to CSF-1 while surprisingly, microglia were not affected. Furthermore, in contrast to the brain, the bone marrow did not express the alternative ligand, IL-34. Yet treatment with IL-34 and co-culture with carcinoma cells partially rescued the anti-CSF-1 effects on MCs. Further, MC-induced invasion was significantly reduced by anti-CSF-1 treatment while microglia-induced invasion was reduced to a lower extend. Moreover, analysis of lung and breast cancer brain metastasis revealed significant differences of CSF-1 and CSF-1R expression. Taken together, our findings demonstrate not only differences of anti-CSF-1 treatment on MCs and microglia but also in the CSF-1 receptor and ligand expression in brain and bone marrow as well as in brain metastasis."],["dc.identifier.doi","10.18632/oncotarget.3855"],["dc.identifier.fs","618466"],["dc.identifier.pmid","26098772"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13609"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/58709"],["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","Antibodies, Monoclonal"],["dc.subject.mesh","Brain"],["dc.subject.mesh","Brain Neoplasms"],["dc.subject.mesh","Breast Neoplasms"],["dc.subject.mesh","Cell Line, Tumor"],["dc.subject.mesh","Cell Movement"],["dc.subject.mesh","Cell Proliferation"],["dc.subject.mesh","Female"],["dc.subject.mesh","Humans"],["dc.subject.mesh","Interleukin-1"],["dc.subject.mesh","MCF-7 Cells"],["dc.subject.mesh","Macrophage Colony-Stimulating Factor"],["dc.subject.mesh","Macrophages"],["dc.subject.mesh","Mice"],["dc.subject.mesh","Mice, Inbred BALB C"],["dc.subject.mesh","Microglia"],["dc.subject.mesh","Monocytes"],["dc.subject.mesh","Neoplasm Invasiveness"],["dc.subject.mesh","Receptor, Macrophage Colony-Stimulating Factor"],["dc.title","Anti-CSF-1 treatment is effective to prevent carcinoma invasion induced by monocyte-derived cells but scarcely by microglia."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1449"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","Oncotarget"],["dc.bibliographiccitation.lastpage","1460"],["dc.bibliographiccitation.volume","4"],["dc.contributor.author","Rietkötter, Eva"],["dc.contributor.author","Menck, Kerstin"],["dc.contributor.author","Bleckmann, Annalen"],["dc.contributor.author","Farhat, Katja"],["dc.contributor.author","Schaffrinski, Meike"],["dc.contributor.author","Schulz, Matthias"],["dc.contributor.author","Hanisch, Uwe-Karsten"],["dc.contributor.author","Binder, Claudia"],["dc.contributor.author","Pukrop, Tobias"],["dc.date.accessioned","2019-07-10T08:11:45Z"],["dc.date.available","2019-07-10T08:11:45Z"],["dc.date.issued","2013-09-01"],["dc.description.abstract","The bisphosphonate zoledronic acid (ZA) significantly reduces complications of bone metastasis by inhibiting resident macrophages, the osteoclasts. Recent clinical trials indicate additional anti-metastatic effects of ZA outside the bone. However, which step of metastasis is influenced and whether thisis due to directtoxicity on cancer cells or inhibition of the tumor promoting microenvironment, is unknown. In particular, tumor-associated and resident macrophages support each step of organ metastasis and could be a crucial target of ZA. Thus, we comparatively investigate the ZA effects on: i) different types of macrophages, ii) on breast cancer cells but also iii) on macrophage-induced invasion. We demonstrate that ZA concentrations reflecting the plasma level affected viability of human macrophages, murine bone marrow-derived macrophages as well as their resident brain equivalents, the microglia, while it did not influence the tested cancer cells. However, the effects on the macrophages subsequently reduced the macrophage/microglia-induced invasiveness of the cancer cells. In line with this, manipulation of microglia by ZA in organotypic brain slice cocultures reduced the tissue invasion by carcinoma cells. The characterization of human macrophages after ZA treatment revealed a phenotype/response shift, in particular after external stimulation. In conclusion, we show that therapeutic concentrations of ZA affect all types of macrophages but not the cancer cells. Thus, anti-metastatic effects of ZA are predominantly caused by modulating the microenvironment. Most importantly, our findings demonstrate that ZA reduced microglia-assisted invasion of cancer cells to the brain tissue, indicating a potential therapeutic role in the prevention of cerebral metastasis."],["dc.identifier.fs","599082"],["dc.identifier.pmid","24036536"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10758"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/60792"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1949-2553"],["dc.relation.orgunit","Universitätsmedizin Göttingen"],["dc.rights","CC BY 3.0"],["dc.rights.uri","http://creativecommons.org/licenses/by/3.0"],["dc.subject.mesh","Animals"],["dc.subject.mesh","Breast Neoplasms"],["dc.subject.mesh","Cell Communication"],["dc.subject.mesh","Cell Line, Tumor"],["dc.subject.mesh","Cell Proliferation"],["dc.subject.mesh","Coculture Techniques"],["dc.subject.mesh","Diphosphonates"],["dc.subject.mesh","Female"],["dc.subject.mesh","Humans"],["dc.subject.mesh","Imidazoles"],["dc.subject.mesh","MCF-7 Cells"],["dc.subject.mesh","Macrophages"],["dc.subject.mesh","Matrix Metalloproteinases"],["dc.subject.mesh","Mice"],["dc.subject.mesh","Microglia"],["dc.subject.mesh","Tumor Microenvironment"],["dc.title","Zoledronic acid inhibits macrophage/microglia-assisted breast cancer cell invasion."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]