Hahn, Heidi Eva

[["dc.bibliographiccitation.firstpage","8785"],["dc.bibliographiccitation.issue","54"],["dc.bibliographiccitation.journal","Oncogene"],["dc.bibliographiccitation.lastpage","8795"],["dc.bibliographiccitation.volume","23"],["dc.contributor.author","Kappler, Roland"],["dc.contributor.author","Bauer, R."],["dc.contributor.author","Calzada-Wack, J."],["dc.contributor.author","Rosemann, M."],["dc.contributor.author","Hemmerlein, Bernhard"],["dc.contributor.author","Hahn, H."],["dc.date.accessioned","2018-11-07T10:43:46Z"],["dc.date.available","2018-11-07T10:43:46Z"],["dc.date.issued","2004"],["dc.description.abstract","Rhabdomyosarcoma (RMS) is a highly malignant tumor that is histologically related to skeletal muscle, yet genetic and molecular lesions underlying its genesis and progression remain largely unknown. In this study we have compared the molecular profiles of two different mouse models of RMS, each associated with a defined primary genetic defect known to play a role in rhabdomyosarco-magenesis in man. We report that RMS of heterozygous Patched1 (Ptch1) mice show less aggressive growth and a greater degree of differentiation than RMS of heterozygous p53 mice. By means of cDNA microarray analysis we demonstrate that RMS in Ptch1 mutants predominantly express a number of myogenic markers, including myogenic differentiation 1, myosin heavy chain, actin, troponin and tropomyosin, as well as genes associated with Hedgehog/Patched signaling like insulin-like growth factor 2, forkhead box gene Foxf1 and the growth arrest and DNA-damage-inducible gene Gadd45a. In sharp contrast, RMS in p53 mutants display higher expression levels of cell cycle-associated genes like cyclin B1, cyclin-dependent kinase 4 and the proliferation marker Ki-67. These results demonstrate that different causative mutations lead to distinct gene expression profiles in RMS, which appear to reflect their different biological characteristics. Our results provide a first step towards a molecular classification of different forms of RMS. If the described differences can be confirmed in human RMS our results will contribute to a new molecular taxonomy of this cancer, which will be critical for gene mutation- and expression-specific therapy."],["dc.identifier.doi","10.1038/sj.onc.1208133"],["dc.identifier.isi","000225165100008"],["dc.identifier.pmid","15480423"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/47133"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","0950-9232"],["dc.title","Profiling the molecular difference between Patched- and p53-dependent rhabdomyosarcoma"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1372"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","Laboratory Investigation"],["dc.bibliographiccitation.lastpage","1386"],["dc.bibliographiccitation.volume","84"],["dc.contributor.author","Laux, Holger"],["dc.contributor.author","Tomer, Raju"],["dc.contributor.author","Mader, Michael T."],["dc.contributor.author","Smida, Jan"],["dc.contributor.author","Budczies, Jan"],["dc.contributor.author","Kappler, Roland"],["dc.contributor.author","Hahn, Heidi"],["dc.contributor.author","Blöchinger, Michaela"],["dc.contributor.author","Schnitzbauer, Udo"],["dc.contributor.author","Eckardt-Schupp, Friederike"],["dc.contributor.author","Höfler, Heinz"],["dc.contributor.author","Becker, Karl-Friedrich"],["dc.date.accessioned","2018-11-07T10:45:18Z"],["dc.date.available","2018-11-07T10:45:18Z"],["dc.date.issued","2004"],["dc.description.abstract","E-cadherin is a cell-cell adhesion molecule and tumor invasion suppressor gene that is frequently altered in human cancers. it interacts through its cytoplasmic domain with beta-catenin which in turn interacts with the Wnt (wingless) signaling pathway. We have compared the effects of different tumor-derived E-cadherin variants with those of normal E-cadherin on Wnt signaling and on genes involved in epithelial mesenchymal transition. We established an in-house cDNA microarray composed of 1105 different, sequence verified cDNA probes corresponding to 899 unique genes that represent the majority of genes known to be involved in cadherin-dependent cell adhesion and signaling ('Adhesion/Signaling Array'). The expression signatures of E-cadherin-negative MDA-MB-435S cancer cells transfected with E-cadherin variants (in frame deletions of exon 8 or 9, D8 or D9, respectively, or a point mutation in exon 8 (D370A)) were compared to that of wild-type E-cadherin (WT) transfected cells. From the differentially expressed genes, we selected 38 that we subsequently analyzed by quantitative real-time RT-PCR and/or Northern Blot. A total of 92% of these were confirmed as differentially expressed. Most of these genes encode proteins of the cytoskeleton, cadherins/integrins, oncogenes and matrix metalloproteases. No significant expression differences of genes downstream of the Wnt-pathway were found, except in E-cadherin D8 transfected cells where upregulation of three Tcf/Lef-transcribed genes was seen. One possible reason for the lack of expression differences of the Tcf/Lef-regulated genes is upregulation of SFRP1 and SFRP3; both of which are competitive inhibitors of the Wnt proteins. Interestingly, known E-cadherin transcriptional repressors, such as SLUG (SNAI2), SIP1 (ZEB2), TWIST1, SNAIL (SNAI1) and ZEB1 (TCF8), but not E12/E47 (TCF3), had a lack of upregulation in cells expressing mutated E-cadherin compared to WT. In conclusion, E-cadherin mutations have no influence on expression of genes involved in Wnt-signaling, but they may promote their own expression by blocking upregulation of E-cadherin repressors."],["dc.identifier.doi","10.1038/labinvest.3700158"],["dc.identifier.isi","000223957300014"],["dc.identifier.pmid","15311212"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/47474"],["dc.language.iso","en"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.relation.issn","0023-6837"],["dc.title","Tumor-associated E-cadherin mutations do not induce Wnt target gene expression, but affect E-cadherin repressors"],["dc.type","review"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Klinische Pädiatrie"],["dc.bibliographiccitation.volume","221"],["dc.contributor.author","Thor, T."],["dc.contributor.author","Heukamp, Lukas Carl"],["dc.contributor.author","Hahn, H."],["dc.contributor.author","Kappler, Roland"],["dc.contributor.author","Buettner, Reinhardt"],["dc.contributor.author","Eggert, Angelika"],["dc.contributor.author","Schramm, Alexander"],["dc.contributor.author","Schulte, Johannes H."],["dc.date.accessioned","2018-11-07T08:30:24Z"],["dc.date.available","2018-11-07T08:30:24Z"],["dc.date.issued","2009"],["dc.format.extent","210"],["dc.identifier.isi","000266161300088"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/16890"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Georg Thieme Verlag Kg"],["dc.publisher.place","Stuttgart"],["dc.relation.issn","0300-8630"],["dc.title","MicroRNAs 221 and 222 in the Pathogenesis of Solid Childhood Tumors"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","793"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","International Journal of Molecular Medicine"],["dc.bibliographiccitation.lastpage","799"],["dc.bibliographiccitation.volume","14"],["dc.contributor.author","Levanat, S."],["dc.contributor.author","Kappler, Roland"],["dc.contributor.author","Hemmerlein, Bernhard"],["dc.contributor.author","Doring, P."],["dc.contributor.author","Musani, V."],["dc.contributor.author","Komar, A."],["dc.contributor.author","Oreskovic, S."],["dc.contributor.author","Pavelic, B."],["dc.contributor.author","Hahn, H."],["dc.date.accessioned","2018-11-07T10:44:18Z"],["dc.date.available","2018-11-07T10:44:18Z"],["dc.date.issued","2004"],["dc.description.abstract","Dermoids belong to the group of developmental cysts and arise from germ cells. Studies on these tumors may therefore increase our understanding of normal germ cell development within different environments and cell lines derived from these lesions may also constitute an important vehicle for studying neoplasia and differentiation. Recently, we investigated the status of the PTCH1 locus in a large get of sporadic non-inflammatory, developmental cystic lesions. Our data showed allelic loss of microsatellite markers in close vicinity to the PTCH1 locus in both odontogenic keratocysts and dentigerous cysts as well as in ovarian dermoid cysts (ODC). In this study, we closely examined the status of the PTCH1 gene in ODCs. Although about 25% of cysts demonstrated LOH at the PTCH1 locus, no nonsense or missense mutations in the coding region of PTCH1 were detected in genomic DNA isolated from any of the ODCs examined by direct sequencing. Staining with PTCH1 and GLI1 antibodies showed that proteins were present in virtually all epithelial linings, with variable staining intensity not correlated with LOH and generally weaker for GLI1. However, cDNA microarray analysis performed on cell lines derived from ODCs did not show any significant alteration in the expression of the analyzed target genes of PTCH1 signaling in any of the cell lines examined, except for CyclinD1 (and several other genes generally not associated with PTCH1 signaling)."],["dc.identifier.isi","000224737700003"],["dc.identifier.pmid","15492847"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/47239"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Professor D A Spandidos"],["dc.relation.issn","1107-3756"],["dc.title","Analysis of the PTCH1 signaling pathway in ovarian dermoids"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","113"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","International Journal of Oncology"],["dc.bibliographiccitation.lastpage","120"],["dc.bibliographiccitation.volume","25"],["dc.contributor.author","Kappler, Roland"],["dc.contributor.author","Hess, I."],["dc.contributor.author","Schlegel, J."],["dc.contributor.author","Hahn, H."],["dc.date.accessioned","2018-11-07T10:47:42Z"],["dc.date.available","2018-11-07T10:47:42Z"],["dc.date.issued","2004"],["dc.description.abstract","Medulloblastoma (MB) is a highly malignant embryonal tumor of the cerebellum with a preferential manifestation in children. Although the majority of MBs occur sporadically, this tumor is also associated with familial cancer syndromes including the nevoid basal cell carcinoma or Gorlin syndrome. Mutations in the tumor suppressor gene PATCHED 1 (PTCH1) have been described in both familial and sporadic cases and inactivation of one Patched 1 (Ptch1) allele in mice promotes development of MB. In order to determine candidate genes involved in tumorigenesis of MB, we have screened tumors of heterozygous Ptch1 mice for differentially expressed genes by means of cDNA microarray technology. Our data show that genes involved in cell cycle, signal transduction and metastasis are transcriptionally upregulated in MB compared to normal cerebellum. Gene ontology analysis reveals cell cycle regulators to be the predominant functional gene class altered in MB of Ptch1 mutants, including D-type cyclins and cyclin-dependent kinase 4. We furthermore describe that overexpression of the growth arrest and DNA-damage-inducible gene Gadd45a is common in Ptch1-associated tumors and Ptch1 null embryos. These results suggest that cDNA microarray technology is a useful toot to discover genes involved in the development of MB that arise in response to a persistent activation of sonic hedgehog (Shh) signaling. This approach may provide novel data for diagnosis, treatment and prevention of human PTCH1-related malignancies."],["dc.identifier.isi","000222162400013"],["dc.identifier.pmid","15201996"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/48022"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Professor D A Spandidos"],["dc.relation.issn","1019-6439"],["dc.title","Transcriptional up-regulation of Gadd45a in Patched-associated medulloblastoma"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","348"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","The Journal of Pathology"],["dc.bibliographiccitation.lastpage","356"],["dc.bibliographiccitation.volume","200"],["dc.contributor.author","Kappler, Roland"],["dc.contributor.author","Calzada-Wack, J."],["dc.contributor.author","Schnitzbauer, U."],["dc.contributor.author","Koleva, M."],["dc.contributor.author","Herwig, A."],["dc.contributor.author","Piontek, G."],["dc.contributor.author","Graedler, F."],["dc.contributor.author","Adamski, J."],["dc.contributor.author","Heinzmann, U."],["dc.contributor.author","Schlegel, J."],["dc.contributor.author","Hemmerlein, Bernhard"],["dc.contributor.author","Quintanilla-Martinez, L."],["dc.contributor.author","Hahn, H."],["dc.date.accessioned","2018-11-07T10:38:01Z"],["dc.date.available","2018-11-07T10:38:01Z"],["dc.date.issued","2003"],["dc.description.abstract","Mutations in the human homologue of Drosophila Patched1 (PTCH1) have been found in several common tumours including basal cell carcinoma, medulloblastoma, and rhabdomyosarcoma (RMS). Medulloblastoma. and RMS are also present in the murine model for Ptch1 deficiency. Tumours in heterozygous Ptch1(neo67/+) mice consistently exhibit elevated transcript levels of the proto-oncogene Gli1, of Ptch1 itself, and of the insulin-like growth factor 2 (Igf2). The present study has investigated additional molecular changes in RMSs of Ptch1 mutant mice by means of microarray analysis find protein expression analysis. The data show activation of the cell survival-promoting Akt/protein kinase B (Pkb). Furthermore, RMSs express increased levels of the anti-apoptotic protein Bcl-2 and of genes and proteins known to inhibit cell proliferation, including Gadd45a and p27(kip1). Taken together, the data suggest that the formation of RMSs in Ptch1 mutants is associated with the ability of tumour cells to resist apoptosis. Copyright (C) 2003 John Wiley Sons, Ltd."],["dc.identifier.doi","10.1002/path.1361"],["dc.identifier.isi","000183931300010"],["dc.identifier.pmid","12845631"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/45710"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","John Wiley & Sons Ltd"],["dc.relation.issn","0022-3417"],["dc.title","Molecular characterization of Patched-associated rhabdomyosarcoma"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","727"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Carcinogenesis"],["dc.bibliographiccitation.lastpage","733"],["dc.bibliographiccitation.volume","23"],["dc.contributor.author","Calzada-Wack, J."],["dc.contributor.author","Kappler, Roland"],["dc.contributor.author","Schnitzbauer, U."],["dc.contributor.author","Richter, T."],["dc.contributor.author","Nathrath, M."],["dc.contributor.author","Rosemann, M."],["dc.contributor.author","Wagner, S. N."],["dc.contributor.author","Hein, Rebecca"],["dc.contributor.author","Hahn, H."],["dc.date.accessioned","2018-11-07T10:30:04Z"],["dc.date.available","2018-11-07T10:30:04Z"],["dc.date.issued","2002"],["dc.description.abstract","Inherited mutations of Patched (PTCH) in the nevoid basal cell carcinoma syndrome (NBCCS) lead to several developmental defects and contribute to tumor formation in a variety of tissues. PTCH mutations have been also identified in sporadic tumors associated with NBCCS including basal cell carcinoma (BCC) and medulloblastoma. Mice heterozygous for Ptch recapitulate the typical developmental symptoms of NBCCS and develop rhabdomyosarcoma (RMS) and medulloblastoma. PTCH is assumed to act as a tumor suppressor gene although inactivation of both alleles has been demonstrated only in a fraction of tumors. We have investigated the status of Ptch in RMS of heterozygous Ptch(neo67/+) mice. Although the wild-type Ptch allele was retained in tumor tissue, the high levels of Ptch mRNA in these tumors result from overexpression of the mutant Ptch transcript. Our results suggest that the wild-type Ptch allele might be selectively silenced in RMS tissue or, alternatively, that haploinsufficiency of Ptch is sufficient to promote RMS formation in mice."],["dc.identifier.doi","10.1093/carcin/23.5.727"],["dc.identifier.isi","000175879000007"],["dc.identifier.pmid","12016144"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/43780"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Oxford Univ Press"],["dc.relation.issn","0143-3334"],["dc.title","Unbalanced overexpression of the mutant allele in murine Patched mutants"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Human Mutation"],["dc.bibliographiccitation.volume","20"],["dc.contributor.author","Calzada-Wack, Julia"],["dc.contributor.author","Schnitzbauer, Udo"],["dc.contributor.author","Walch, Axel"],["dc.contributor.author","Wurster, Karl-Heinz"],["dc.contributor.author","Kappler, Roland"],["dc.contributor.author","Nathrath, Michaela"],["dc.contributor.author","Hahn, Heidi"],["dc.date.accessioned","2018-11-07T10:05:12Z"],["dc.date.available","2018-11-07T10:05:12Z"],["dc.date.issued","2002"],["dc.description.abstract","Inherited mutations of the human tumor suppressor gene Patched (PTCH) lead to an autosomal dominant disorder known as Nevoid Basal Cell Carcinoma Syndrome (NBCCS). The syndrome is characterized by a combination of developmental abnormalities and a predisposition to tumor formation. Tumors in patients with NBCCS include basal cell carcinoma, medulloblastoma, fibroma and rhabdomyosarcoma (RMS). RMS are also present in 15 % of mice haplodeficient for Ptch. To investigate whether mutations in PTCH are a general feature in rhabdomyosarcomagenesis we sequenced the protein-coding region in sporadic human cases of these tumors. For this purpose we first determined the distribution and frequency of polymorphisms in 23 exons of PTCH in 48 healthy caucasians. Ten new polymorphisms were identified (IVS11 + 15-17del AAA; IVS14 + 25T>C; 2485G>A; IVS15 + 9G>C; IVS17 + 21A>G; 3033T>C; 3149T>C; 3387T>C; 3617G>A; 4080C>T). Next, the PTCH coding region in 14 RMS was sequenced. Whereas one case with LOH at the PTCH locus was detected, none of the cases showed nonsense or missense mutations in the coding region of PTCH. These data do not support the existence of frequent mutations in the protein-coding region of PTCH in RMS. (C) 2002 Wiley-Liss, Inc."],["dc.description.sponsorship","BioFuture-Grant of the German Ministry for Education and Research BMBF"],["dc.identifier.doi","10.1002/humu.9056"],["dc.identifier.isi","000209087900009"],["dc.identifier.pmid","12204003"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/38857"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","1098-1004"],["dc.relation.issn","1059-7794"],["dc.title","Analysis of the PTCH Coding Region in Human Rhabdomyosarcoma"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","405"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","International Journal of Oncology"],["dc.bibliographiccitation.lastpage","412"],["dc.bibliographiccitation.volume","31"],["dc.contributor.author","Eichenmueller, Melanie"],["dc.contributor.author","Bauer, Regine"],["dc.contributor.author","von Schweinitz, Dietrich"],["dc.contributor.author","Hahn, Heidi"],["dc.contributor.author","Kappler, Roland"],["dc.date.accessioned","2018-11-07T11:00:06Z"],["dc.date.available","2018-11-07T11:00:06Z"],["dc.date.issued","2007"],["dc.description.abstract","The tumor suppressor gene PATCHED1 (PTCH1) is a member of the hedgehog signaling pathway and causatively associated with several human sporadic and familial cancers, including those of the skin, muscle and brain. Inactivation of one Ptch1 allele in the mouse results in the development of medulloblastoma and rhabdomyosarcoma (RMS), the latter being a malignant tumor of skeletal muscle origin. To identify genes involved in the pathogenesis of Ptch1-associated RMS, we have monitored the expression of 588 genes in RMS and normal skeletal muscle (SM) of heterozygous Ptch1(neo67/+) mice using cDNA array technology. RMS displayed increased transcript levels of several genes such as transforming growth factor-beta l (Tgfb1), insulin-like growth factor 2 (Igf2), villin 2 (Vil2), integrin beta 1 (Itgb1), Sloan-Kettering viral oncogene homolog (Ski), and insulin-like growth factor binding protein 3 (Igfbp3), as well as numerous genes coding for structural components of myogenic cells such as myosin light polypeptide 4 (My14), myosin light polypeptide 6 (My16), and vimentin (Vim). Detailed promoter analysis revealed a putative Gli binding site in the second promoter region (P2) of the murine Tgfb1 gene. However, using reporter assay we show that the P2 promoter is not responsive to hedgehog signaling. We furthermore describe that Tgfb1 expression could not be activated in C2C12 myoblasts in the presence of murine Shh-N peptide and that Tgfb1 is equally expressed in both wild-type and Ptch1-deficient mouse embryos. In line with this, TGFB1 was strongly expressed in human RMS cell lines independently of the GL11 expression status. In summary, our results suggest that aberrant expression of Tgfb1 may be involved in RMS development in a way that is independent of hedgehog signaling."],["dc.identifier.isi","000248286000020"],["dc.identifier.pmid","17611698"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/50857"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Professor D A Spandidos"],["dc.relation.issn","1019-6439"],["dc.title","Hedgehog-independent overexpression of transforming growth factor-beta 1 in rhabdomyosarcoma of Patched1 mutant mice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]