Hahn, Heidi Eva

[["dc.bibliographiccitation.firstpage","2179"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","Molecular Cancer Therapeutics"],["dc.bibliographiccitation.lastpage","2188"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Uhmann, Anja"],["dc.contributor.author","Niemann, Hannah"],["dc.contributor.author","Lammering, Berenice"],["dc.contributor.author","Henkel, Cornelia"],["dc.contributor.author","Hess, Ina"],["dc.contributor.author","Nitzki, Frauke"],["dc.contributor.author","Fritsch, Anne"],["dc.contributor.author","Pruefer, Nicole"],["dc.contributor.author","Rosenberger, Albert"],["dc.contributor.author","Dullin, Christian"],["dc.contributor.author","Schraepler, Anke"],["dc.contributor.author","Reifenberger, Julia"],["dc.contributor.author","Schweyer, Stefan"],["dc.contributor.author","Pietsch, Torsten"],["dc.contributor.author","Strutz, Frank M."],["dc.contributor.author","Schulz-Schaeffer, Walter J."],["dc.contributor.author","Hahn, Heidi"],["dc.date.accessioned","2018-11-07T08:50:18Z"],["dc.date.available","2018-11-07T08:50:18Z"],["dc.date.issued","2011"],["dc.description.abstract","Activation of the Hedgehog (Hh)-signaling pathway due to deficiency in the Hh receptor Patched1 (Ptch) is the pivotal defect leading to formation of basal cell carcinoma (BCC). Recent reports provided evidence of Ptch-dependent secretion of vitamin D(3)-related compound, which functions as an endogenous inhibitor of Hh signaling by repressing the activity of the signal transduction partner of Ptch, Smoothened (Smo). This suggests that Ptch-deficient tumor cells are devoid of this substance, which in turn results in activation of Hh-signaling. Here, we show that the application of the physiologically active form of vitamin D(3), calcitriol, inhibits proliferation and growth of BCC of Ptch mutant mice in vitro and in vivo. This is accompanied by the activation of the vitamin D receptor (Vdr) and induction of BCC differentiation. In addition, calcitriol inhibits Hh signaling at the level of Smo in a Vdr-independent manner. The concomitant antiproliferative effects on BCC growth are stronger than those of the Hh-specific inhibitor cyclopamine, even though the latter more efficiently inhibits Hh signaling. Taken together, we show that exogenous supply of calcitriol controls the activity of 2 independent pathways, Hh and Vdr signaling, which are relevant to tumorigenesis and tumor treatment. These data suggest that calcitriol could be a therapeutic option in the treatment of BCC, the most common tumor in humans. Mol Cancer Ther; 10(11); 2179-88. (C) 2011 AACR."],["dc.identifier.doi","10.1158/1535-7163.MCT-11-0422"],["dc.identifier.isi","000296791300032"],["dc.identifier.pmid","21878656"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/21665"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Assoc Cancer Research"],["dc.relation.issn","1535-7163"],["dc.title","Antitumoral Effects of Calcitriol in Basal Cell Carcinomas Involve Inhibition of Hedgehog Signaling and Induction of Vitamin D Receptor Signaling and Differentiation"],["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.journal","Oncogene"],["dc.contributor.author","Bauer, Julia"],["dc.contributor.author","Cuvelier, Nicole"],["dc.contributor.author","Ragab, Nada"],["dc.contributor.author","Simon-Keller, Katja"],["dc.contributor.author","Nitzki, Frauke"],["dc.contributor.author","Geyer, Natalie"],["dc.contributor.author","Botermann, Dominik S."],["dc.contributor.author","Elmer, Dominik P."],["dc.contributor.author","Rosenberger, Albert"],["dc.contributor.author","Hahn, Heidi"],["dc.date.accessioned","2021-07-05T15:00:28Z"],["dc.date.available","2021-07-05T15:00:28Z"],["dc.date.issued","2021"],["dc.description.abstract","Abstract A prototypic pediatric cancer that frequently shows activation of RAS signaling is embryonal rhabdomyosarcoma (ERMS). ERMS also show aberrant Hedgehog (HH)/GLI signaling activity and can be driven by germline mutations in this pathway. We show, that in ERMS cell lines derived from sporadic tumors i.e. from tumors not caused by an inherited genetic variant, HH/GLI signaling plays a subordinate role, because oncogenic mutations in HRAS , KRAS , or NRAS (collectively named oncRAS) inhibit the main HH target GLI1 via the MEK/ERK-axis, but simultaneously increase proliferation and tumorigenicity. oncRAS also modulate expression of stem cell markers in an isoform- and context-dependent manner. In Hh -driven murine ERMS that are caused by a Patched mutation, oncHRAS and mainly oncKRAS accelerate tumor development, whereas oncNRAS induces a more differentiated phenotype. These features occur when the oncRAS mutations are induced at the ERMS precursor stage, but not when induced in already established tumors. Moreover, in contrast to what is seen in human cell lines, oncRAS mutations do not alter Hh signaling activity and marginally affect expression of stem cell markers. Together, all three oncRAS mutations seem to be advantageous for ERMS cell lines despite inhibition of HH signaling and isoform-specific modulation of stem cell markers. In contrast, oncRAS mutations do not inhibit Hh-signaling in Hh-driven ERMS. In this model, oncRAS mutations seem to be advantageous for specific ERMS populations that occur within a specific time window during ERMS development. In addition, this window may be different for individual oncRAS isoforms, at least in the mouse."],["dc.description.abstract","Abstract A prototypic pediatric cancer that frequently shows activation of RAS signaling is embryonal rhabdomyosarcoma (ERMS). ERMS also show aberrant Hedgehog (HH)/GLI signaling activity and can be driven by germline mutations in this pathway. We show, that in ERMS cell lines derived from sporadic tumors i.e. from tumors not caused by an inherited genetic variant, HH/GLI signaling plays a subordinate role, because oncogenic mutations in HRAS , KRAS , or NRAS (collectively named oncRAS) inhibit the main HH target GLI1 via the MEK/ERK-axis, but simultaneously increase proliferation and tumorigenicity. oncRAS also modulate expression of stem cell markers in an isoform- and context-dependent manner. In Hh -driven murine ERMS that are caused by a Patched mutation, oncHRAS and mainly oncKRAS accelerate tumor development, whereas oncNRAS induces a more differentiated phenotype. These features occur when the oncRAS mutations are induced at the ERMS precursor stage, but not when induced in already established tumors. Moreover, in contrast to what is seen in human cell lines, oncRAS mutations do not alter Hh signaling activity and marginally affect expression of stem cell markers. Together, all three oncRAS mutations seem to be advantageous for ERMS cell lines despite inhibition of HH signaling and isoform-specific modulation of stem cell markers. In contrast, oncRAS mutations do not inhibit Hh-signaling in Hh-driven ERMS. In this model, oncRAS mutations seem to be advantageous for specific ERMS populations that occur within a specific time window during ERMS development. In addition, this window may be different for individual oncRAS isoforms, at least in the mouse."],["dc.identifier.doi","10.1038/s41388-021-01904-4"],["dc.identifier.pii","1904"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/87833"],["dc.language.iso","en"],["dc.notes.intern","DOI Import DOI-Import GROB-441"],["dc.relation.eissn","1476-5594"],["dc.relation.issn","0950-9232"],["dc.title","Context-dependent modulation of aggressiveness of pediatric tumors by individual oncogenic RAS isoforms"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Frontiers in Genetics"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Pyczek, Joanna"],["dc.contributor.author","Khizanishvili, Natalia"],["dc.contributor.author","Kuzyakova, Maria"],["dc.contributor.author","Zabel, Sebastian"],["dc.contributor.author","Bauer, Julia"],["dc.contributor.author","Nitzki, Frauke"],["dc.contributor.author","Emmert, Steffen"],["dc.contributor.author","Schön, Michael P."],["dc.contributor.author","Boukamp, Petra"],["dc.contributor.author","Schildhaus, Hans-Ulrich"],["dc.contributor.author","Uhmann, Anja"],["dc.contributor.author","Hahn, Heidi"],["dc.date.accessioned","2020-12-10T18:44:24Z"],["dc.date.available","2020-12-10T18:44:24Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.3389/fgene.2019.01185"],["dc.identifier.eissn","1664-8021"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16829"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/78434"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Regulation and Role of GLI1 in Cutaneous Squamous Cell Carcinoma Pathogenesis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Anticancer Research"],["dc.bibliographiccitation.volume","31"],["dc.contributor.author","Uhmann, Anja"],["dc.contributor.author","Niemann, Hannah"],["dc.contributor.author","Lammering, Berenice"],["dc.contributor.author","Henkel, Cornelia"],["dc.contributor.author","Hess, Ina"],["dc.contributor.author","Nitzki, Frauke"],["dc.contributor.author","Fritsch, Anne"],["dc.contributor.author","Rosenberger, Albert"],["dc.contributor.author","Dullin, Christian"],["dc.contributor.author","Schraepler, Anke"],["dc.contributor.author","Reifenberger, Julia"],["dc.contributor.author","Schweyer, Stefan"],["dc.contributor.author","Pietsch, Torsten"],["dc.contributor.author","Strutz, Frank M."],["dc.contributor.author","Schulz-Schaeffer, Walter J."],["dc.contributor.author","Hahn, Heidi"],["dc.date.accessioned","2018-11-07T08:57:14Z"],["dc.date.available","2018-11-07T08:57:14Z"],["dc.date.issued","2011"],["dc.format.extent","1499"],["dc.identifier.isi","000290292000081"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/23344"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Int Inst Anticancer Research"],["dc.publisher.place","Athens"],["dc.relation.issn","0250-7005"],["dc.title","ANTITUMOR EFFECTS OF CALCITRIOL IN PATCHED1-ASSOCIATED BASAL CELL CARCINOMA INVOLVES INHIBITION OF HEDGEHOG SIGNALING AND INDUCTION OF DIFFERENTIATION"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","134"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Gastroenterology"],["dc.bibliographiccitation.lastpage","U256"],["dc.bibliographiccitation.volume","144"],["dc.contributor.author","Pelczar, Penelope"],["dc.contributor.author","Zibat, Arne"],["dc.contributor.author","van Dop, Willemijn A."],["dc.contributor.author","Heijmans, Jarom"],["dc.contributor.author","Bleckmann, Annalen"],["dc.contributor.author","Gruber, Wolfgang"],["dc.contributor.author","Nitzki, Frauke"],["dc.contributor.author","Uhmann, Anja"],["dc.contributor.author","Guijarro, Maria V."],["dc.contributor.author","Hernando, Eva"],["dc.contributor.author","Dittmann, Kai"],["dc.contributor.author","Wienands, Juergen"],["dc.contributor.author","Dressel, Ralf"],["dc.contributor.author","Wojnowski, Leszek"],["dc.contributor.author","Binder, Claudia"],["dc.contributor.author","Taguchi, Takahiro"],["dc.contributor.author","Beißbarth, Tim"],["dc.contributor.author","Hogendoorn, Pancras Cornelis Wilhelmus"],["dc.contributor.author","Antonescu, Cristina R."],["dc.contributor.author","Rubin, Brian P."],["dc.contributor.author","Schulz-Schaeffer, Walter Joachim"],["dc.contributor.author","Aberger, Fritz"],["dc.contributor.author","van den Brink, Gijs R."],["dc.contributor.author","Hahn, Heidi Eva"],["dc.date.accessioned","2018-11-07T09:30:42Z"],["dc.date.available","2018-11-07T09:30:42Z"],["dc.date.issued","2013"],["dc.description.abstract","BACKGROUND & AIMS: A fraction of gastrointestinal stromal tumor (GIST) cells overexpress the platelet-derived growth factor receptor (PDGFR) A, although most overexpress KIT. It is not known if this is because these receptor tyrosine kinases have complementary oncogenic potential, or because of heterogeneity in the cellular origin of GIST. Little also is known about why Hedgehog (HH) signaling is activated in some GIST. HH binds to and inactivates the receptor protein patched homolog (PTCH). METHODS: Ptch was conditionally inactivated in mice (to achieve constitutive HH signaling) using a Cre recombinase regulated by the lysozyme M promoter. Cre-expressing cells were traced using R26R-LacZ reporter mice. Tumors were characterized by in situ hybridization, immunohistochemistry, immunoblot, and quantitative reverse-transcriptase polymerase chain reaction analyses. Cell transformation was assessed by soft agar assay. RESULTS: Loss of Ptch from lysozyme M-expressing cells resulted in the development of tumors of GIST-like localization and histology; these were reduced when mice were given imatinib, a drug that targets KIT and PDGFRA. The Hh signaling pathway was activated in the tumor cells, and Pdgfr alpha, but not Kit, was overexpressed and activated. Lineage tracing revealed that Cre-expressing intestinal cells were Kit-negative. These cells sometimes expressed Pdgfr alpha and were located near Kit-positive interstitial cells of Cajal. In contrast to KIT, activation of PDGFRA increased anchorage-independent proliferation and was required for tumor formation in mice by cells with activated HH signaling. CONCLUSIONS: Inactivation of Ptch in mice leads to formation of GIST-like tumors that express Pdgfr alpha, but not Kit. Activation of Pdgfr alpha signaling appears to facilitate tumorigenesis."],["dc.identifier.doi","10.1053/j.gastro.2012.09.061"],["dc.identifier.isi","000312965100034"],["dc.identifier.pmid","23041331"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/31367"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","W B Saunders Co-elsevier Inc"],["dc.relation.issn","0016-5085"],["dc.title","Inactivation of Patched1 in Mice Leads to Development of Gastrointestinal Stromal-Like Tumors That Express Pdgfr alpha but Not Kit"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2620"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","Journal of Investigative Dermatology"],["dc.bibliographiccitation.lastpage","2629"],["dc.bibliographiccitation.volume","134"],["dc.contributor.author","Uhmann, Anja"],["dc.contributor.author","Hess, Ina"],["dc.contributor.author","Frommhold, Anke"],["dc.contributor.author","Koenig, Simone"],["dc.contributor.author","Zabel, Sebastian"],["dc.contributor.author","Nitzki, Frauke"],["dc.contributor.author","Dittmann, Kai"],["dc.contributor.author","Luehder, Fred"],["dc.contributor.author","Christiansen, Hans"],["dc.contributor.author","Reifenberger, Julia"],["dc.contributor.author","Schulz-Schaeffer, Walter J."],["dc.contributor.author","Hahn, Heidi"],["dc.date.accessioned","2018-11-07T09:34:46Z"],["dc.date.available","2018-11-07T09:34:46Z"],["dc.date.issued","2014"],["dc.description.abstract","The development of basal cell carcinoma (BCC), the most frequently diagnosed tumor among persons with European ancestry, is closely linked to mutations in the Hedgehog (Hh) receptor and tumor suppressor Patched1 (Ptch). Using Ptch(flox/flox)CD4Cre(+/-) mice, in which Ptch was ablated in CD4Cre-expressing cells, we demonstrate that the targeted cells can give rise to BCC after treatment with DMBA (7,12-dimethylbenz(a)anthracene)/TPA (12-O-tetradecanoylphorbol-13-acetate), but not after wounding of the skin. In addition, in this model, BCC are not caused by malfunctioning of Ptch-deficient T cells, as BCC did not develop when bone marrow (BM) of Ptch(flox/flox)CD4Cre(+/-) mice was transplanted into Ptch wild-type mice. Instead, lineage-tracing experiments and flow cytometric analyses suggest that the tumors are initiated from rare Ptch-deficient stem cell-like cells of the epidermis that express CD4. As DMBA/TPA is a prerequisite for BCC development in this model, the initiated cells need a second stimulus for expansion and tumor formation. However, in contrast to papilloma, this stimulus seems to be unrelated to alterations in the Ras signaling cascade. Together, these data suggest that biallelic loss of Ptch in CD4(+) cells does not suffice for BCC formation and that BCC formation requires a second so far unknown event, at least in the Ptch(flox/flox)CD4Cre(+/-) BCC mouse model."],["dc.identifier.doi","10.1038/jid.2014.157"],["dc.identifier.isi","000342200400023"],["dc.identifier.pmid","24662765"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/32249"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Inc"],["dc.relation.issn","1523-1747"],["dc.relation.issn","0022-202X"],["dc.title","DMBA/TPA Treatment Is Necessary for BCC Formation from Patched Deficient Epidermal Cells in Ptch(flox/flox)CD4Cre(+/-) Mice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1814"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Blood"],["dc.bibliographiccitation.lastpage","1823"],["dc.bibliographiccitation.volume","110"],["dc.contributor.author","Uhmann, Anja"],["dc.contributor.author","Dittmann, Kai"],["dc.contributor.author","Nitzki, Frauke"],["dc.contributor.author","Dressel, Ralf"],["dc.contributor.author","Koleva, Milena"],["dc.contributor.author","Frommhold, Anke"],["dc.contributor.author","Zibat, Arne"],["dc.contributor.author","Binder, Claudia"],["dc.contributor.author","Adham, Ibrahim M."],["dc.contributor.author","Nitsche, Mirko"],["dc.contributor.author","Heller, Tanja"],["dc.contributor.author","Armstrong, Victor"],["dc.contributor.author","Schulz-Schaeffer, Walter J."],["dc.contributor.author","Wienands, Juergen"],["dc.contributor.author","Hahn, Heidi"],["dc.date.accessioned","2018-11-07T10:58:34Z"],["dc.date.available","2018-11-07T10:58:34Z"],["dc.date.issued","2007"],["dc.description.abstract","A first step in hematopoiesis is the specification of the lymphoid and myeloid lineages from multipotent progenitor cells in the bone marrow. Using a conditional ablation strategy in adult mice, we show that this differentiation step requires Patched (Ptch), the cell surface-bound receptor for Hedgehog (Hh). In the absence of Ptch, the development of T- and B-lymphoid lineages is blocked at the level of the common lymphoid progenitor in the bone marrow. Consequently, the generation of peripheral T and B cells is abrogated. Cells of the myeloid lineage develop normally in Ptch mutant mice. Finally, adoptive transfer experiments identified the stromal cell compartment as a critical Ptch-dependent inducer of lymphoid versus myeloid lineage commitment. Our data show that Ptch acts as a master switch for proper diversification of hematopoietic stem cells in the adult organism."],["dc.identifier.doi","10.1182/blood-2007-02-075648"],["dc.identifier.isi","000249671700022"],["dc.identifier.pmid","17536012"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/50494"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Soc Hematology"],["dc.relation.issn","0006-4971"],["dc.title","The Hedgehog receptor Patched controls lymphoid lineage commitment"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","918"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Carcinogenesis"],["dc.bibliographiccitation.lastpage","926"],["dc.bibliographiccitation.volume","30"],["dc.contributor.author","Zibat, Arne"],["dc.contributor.author","Uhmann, Anja"],["dc.contributor.author","Nitzki, Frauke"],["dc.contributor.author","Wijgerde, Mark"],["dc.contributor.author","Frommhold, Anke"],["dc.contributor.author","Heller, Tanja"],["dc.contributor.author","Armstrong, Victor"],["dc.contributor.author","Wojnowski, Leszek"],["dc.contributor.author","Quintanilla-Martinez, Leticia"],["dc.contributor.author","Reifenberger, Julia"],["dc.contributor.author","Schulz-Schaeffer, Walter J."],["dc.contributor.author","Hahn, Heidi"],["dc.date.accessioned","2018-11-07T08:28:59Z"],["dc.date.available","2018-11-07T08:28:59Z"],["dc.date.issued","2009"],["dc.description.abstract","Mutations in Patched (PTCH) have been associated with tumors characteristic both for children [medulloblastoma (MB) and rhabdomyosarcoma (RMS)] and for elderly [basal cell carcinoma (BCC)]. The determinants of the variability in tumor onset and histology are unknown. We investigated the effects of the time-point and dosage of Ptch inactivation on tumor spectrum using conditional Ptch-knockout mice. Ptch heterozygosity induced prenatally resulted in the formation of RMS, which was accompanied by the silencing of the remaining wild-type Ptch allele. In contrast, RMS was observed neither after mono- nor biallelic postnatal deletion of Ptch. Postnatal biallelic deletion of Ptch led to BCC precancerous lesions of the gastrointestinal epithelium and mesenteric tumors. Hamartomatous gastrointestinal cystic tumors were induced by monoallelic, but not biallelic Ptch mutations, independently of the time-point of mutation induction. These data suggest that the expressivity of Ptch deficiency is largely determined by the time-point, the gene dose and mode of Ptch inactivation. Furthermore, they point to key differences in the tumorigenic mechanisms underlying adult and childhood tumors. The latter ones are unique among all tumors since their occurrence decreases rather than increases with age. A better understanding of mechanisms underlying this ontological restriction is of potential therapeutic value."],["dc.identifier.doi","10.1093/carcin/bgp068"],["dc.identifier.isi","000266708200003"],["dc.identifier.pmid","19321799"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/16546"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Oxford Univ Press"],["dc.relation.issn","0143-3334"],["dc.title","Time-point and dosage of gene inactivation determine the tumor spectrum in conditional Ptch knockouts"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]