Hahn, Heidi Eva

[["dc.bibliographiccitation.firstpage","1567"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","International Journal of Oncology"],["dc.bibliographiccitation.lastpage","1575"],["dc.bibliographiccitation.volume","27"],["dc.contributor.author","Uhmann, Anja"],["dc.contributor.author","Ferch, U."],["dc.contributor.author","Bauer, R."],["dc.contributor.author","Tauber, S."],["dc.contributor.author","Arziman, Z."],["dc.contributor.author","Chen, C."],["dc.contributor.author","Hemmerlein, Bernhard"],["dc.contributor.author","Wojnowski, Leszek"],["dc.contributor.author","Hahn, H."],["dc.date.accessioned","2018-11-07T10:53:52Z"],["dc.date.available","2018-11-07T10:53:52Z"],["dc.date.issued","2005"],["dc.description.abstract","Mutations of the Sonic hedgehog (SHH) receptor, Patched I (PITCH I), have been identified in a variety of tumors. PTCH1 is usually considered to be a tumor suppressor gene. However, one normal allele is retained in many tumors. We investigated the mechanism of tumorigenesis in murine heterozygous Ptch1 knock-out mice. Here we show that Ptch1 transcripts, which are consistently overexpressed in tumors in these mice, are derived predominantly from the mutated allele. These transcripts give rise to a mutant protein incapable of pathway inhibition. In contrast, the expression of wild-type transcripts in the tumor is reduced. The transcriptional activity of a Ptch1 promoter is sensitive to methylation. Based on these results, we propose a model, in which tumorigenesis begins with the transcriptional silencing of one PTCH1/Ptch1 allele. This alone has no functional consequences. Upon mutational inactivation of the other allele, the resulting loss of PTCH1/Ptch1 function activates PTCH1/Ptch1 transcription from the non-silenced, i.e. the mutant, allele. These events can occur in an opposite order. This model is consistent with the expression of PTCH1/Ptch1-derived transcripts and proteins found in tumors, with the sensitivity of the murine Ptch1 promoter to methylation, and with the recently reported effect of demethylating agents on Ptch1 expression. These latter agents could be effective in treatment of, at least, some tumors associated with loss of PTCH1 function."],["dc.identifier.isi","000233575100014"],["dc.identifier.pmid","16273213"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/49440"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Professor D A Spandidos"],["dc.relation.issn","1019-6439"],["dc.title","A model for PTCH1/Ptch1-associated tumors comprising mutational inactivation and gene silencing"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","The Journal of Immunology"],["dc.bibliographiccitation.volume","183"],["dc.contributor.author","Uhmann, Anja"],["dc.contributor.author","Dittmann, Kai"],["dc.contributor.author","Wienands, Juergen"],["dc.contributor.author","Hahn, Heidi"],["dc.date.accessioned","2018-11-07T11:25:03Z"],["dc.date.available","2018-11-07T11:25:03Z"],["dc.date.issued","2009"],["dc.format.extent","2891"],["dc.identifier.doi","10.4049/jimmunol.0990063"],["dc.identifier.isi","000269391400001"],["dc.identifier.pmid","19696426"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/56544"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Assoc Immunologists"],["dc.relation.issn","0022-1767"],["dc.title","Comment on \"Direct Hematological Toxicity and Illegitimate Chromosomal Recombination Caused by the Systemic Activation of CreER(T2)\""],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.subtype","letter_note"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","European Journal of Gastroenterology & Hepatology"],["dc.bibliographiccitation.volume","20"],["dc.contributor.author","van Dop, Willemijn A."],["dc.contributor.author","Uhmann, Anja"],["dc.contributor.author","Wijgerde, Mark"],["dc.contributor.author","Offerhaus, G. Johan A."],["dc.contributor.author","Boeckxstaens, Guy E."],["dc.contributor.author","Weerman, Marius A. van den Bergh"],["dc.contributor.author","Hommes, Daan W."],["dc.contributor.author","Hardwick, J. C."],["dc.contributor.author","Hahn, H."],["dc.contributor.author","van den Brink, Gijs R."],["dc.date.accessioned","2018-11-07T11:13:23Z"],["dc.date.available","2018-11-07T11:13:23Z"],["dc.date.issued","2008"],["dc.format.extent","A73"],["dc.identifier.isi","000257620600200"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/53879"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Lippincott Williams & Wilkins"],["dc.publisher.place","Philadelphia"],["dc.relation.issn","0954-691X"],["dc.title","Depletion of the colonic stem cell compartment upon conditional activation of the Hedgehog pathway"],["dc.type","conference_abstract"],["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","Gut"],["dc.bibliographiccitation.lastpage","357"],["dc.bibliographiccitation.volume","62"],["dc.contributor.author","van Dop, Willemijn A."],["dc.contributor.author","Rosekrans, Sanne L."],["dc.contributor.author","Uhmann, Anja"],["dc.contributor.author","Jaks, Viljar"],["dc.contributor.author","Offerhaus, G. Johan A."],["dc.contributor.author","Weerman, Marius A. van den Bergh"],["dc.contributor.author","Kasper, Maria"],["dc.contributor.author","Heijmans, Jarom"],["dc.contributor.author","Hardwick, James C. H."],["dc.contributor.author","Verspaget, Hein W."],["dc.contributor.author","Hommes, Daan W."],["dc.contributor.author","Toftgard, Rune"],["dc.contributor.author","Hahn, Heidi"],["dc.contributor.author","van den Brink, Gijs R."],["dc.date.accessioned","2018-11-07T09:27:54Z"],["dc.date.available","2018-11-07T09:27:54Z"],["dc.date.issued","2013"],["dc.description.abstract","Objective In the intestine Hedgehog (Hh) signalling is directed from epithelium to mesenchyme and negatively regulates epithelial precursor cell fate. The role of Hh signalling in the oesophagus has not been studied in vivo. Here the authors examined the role of Hh signalling in epithelial homeostasis of oesophagus. Design The authors used transgenic mice in which the Hh receptor Patched1 (Ptch1) could be conditionally inactivated in a body-wide manner and mice in which Gli1 could be induced specifically in the epithelium of the skin and oesophagus. Effects on epithelial homeostasis of the oesophagus were examined using immunohistochemistry, in situ hybridisation, transmission electron microscopy and real-time PCR. Hh signalling was examined in patients with oesophageal squamous cell carcinoma (SCC) by quantitative real-time PCR. Results Sonic Hh is signalled in an autocrine manner in the basal layer of the oesophagus. Activation of Hh signalling resulted in an expansion of the epithelial precursor cell compartment and failure of epithelial maturation and migration. Levels of Hh targets GLI1, HHIP and PTCH1 were increased in SCC compared with normal tissue from the same patients. Conclusion Here the authors find that Hh signalling positively regulates the precursor cell compartment in the oesophageal epithelium in an autocrine manner. Since Hh signalling targets precursor cells in the oesophageal epithelium and signalling is increased in SCCs, Hh signalling may be involved in oesophageal SCC formation."],["dc.identifier.doi","10.1136/gutjnl-2011-301141"],["dc.identifier.isi","000314631900004"],["dc.identifier.pmid","22504664"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/30651"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Bmj Publishing Group"],["dc.relation.issn","0017-5749"],["dc.title","Hedgehog signalling stimulates precursor cell accumulation and impairs epithelial maturation in the murine oesophagus"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","19614"],["dc.bibliographiccitation.issue","32"],["dc.bibliographiccitation.journal","Journal of Biological Chemistry"],["dc.bibliographiccitation.lastpage","19628"],["dc.bibliographiccitation.volume","290"],["dc.contributor.author","Linder, Benedikt"],["dc.contributor.author","Weber, Susanne"],["dc.contributor.author","Dittmann, Kai"],["dc.contributor.author","Adamski, Jerzy"],["dc.contributor.author","Hahn, Heidi"],["dc.contributor.author","Uhmann, Anja"],["dc.date.accessioned","2018-11-07T09:53:20Z"],["dc.date.available","2018-11-07T09:53:20Z"],["dc.date.issued","2015"],["dc.description.abstract","The Patched1 (Ptch)-mediated inhibition of Smoothened (Smo) is still an open question. However, a direct Ptch/Smo interaction has been excluded, Smo modulators were identified, but the endogenous signal transmitting molecule remains undiscovered. Here, we demonstrate that calcitriol, the hormonally active form of vitamin D-3, is an excellent candidate for transmission of Ptch/Smo interaction. Our study reveals that Ptch expression is sufficient to release calcitriol from the cell and that calcitriol inhibits Smo action and ciliary translocation by acting on a site distinct from the 7-transmembrane domain or the cysteine-rich domain. Moreover calcitriol strongly synergizes with itraconazole (ITZ) in Smo inhibition, which did not result from elevated calcitriol bioavailability due to ITZ-mediated 24-hydroxylase inhibition but rather from a direct interaction of the compounds at the level of Smo. Together, we suggest that calcitriol represents a possible endogenous transmitter of Ptch/Smo interaction. Moreover calcitriol or calcitriol derivatives combined with ITZ might be a treatment option of Hedgehog-associated cancers."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft [UH 228/2-1, UH228/2-2]"],["dc.identifier.doi","10.1074/jbc.M115.646141"],["dc.identifier.isi","000359364600023"],["dc.identifier.pmid","26126827"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/36311"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Soc Biochemistry Molecular Biology Inc"],["dc.relation.issn","1083-351X"],["dc.relation.issn","0021-9258"],["dc.title","A Functional and Putative Physiological Role of Calcitriol in Patched1/Smoothened Interaction"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","47"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Klinische Pädiatrie"],["dc.bibliographiccitation.lastpage","48"],["dc.bibliographiccitation.volume","223"],["dc.contributor.author","Hahn, H."],["dc.contributor.author","Nitzki, F."],["dc.contributor.author","Zibat, Arne"],["dc.contributor.author","Uhmann, Anja"],["dc.contributor.author","Ecke, I."],["dc.contributor.author","Rosenberger, Albert"],["dc.contributor.author","Witt, Olaf"],["dc.contributor.author","Schulz-Schaeffer, Walter J."],["dc.date.accessioned","2018-11-07T09:00:30Z"],["dc.date.available","2018-11-07T09:00:30Z"],["dc.date.issued","2011"],["dc.identifier.doi","10.1055/s-0030-1270305"],["dc.identifier.isi","000287627100024"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/24177"],["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","Hedgehog Signaling: A Therapeutic Target in Embryonal Rhabdomyosarcoma?"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","International Journal of Oncology"],["dc.bibliographiccitation.volume","61"],["dc.contributor.author","Ragab, Nada"],["dc.contributor.author","Bauer, Julia"],["dc.contributor.author","Uhmann, Anja"],["dc.contributor.author","Marx, Alexander"],["dc.contributor.author","Hahn, Heidi"],["dc.contributor.author","Simon-Keller, Katja"],["dc.date.accessioned","2022-09-01T09:51:17Z"],["dc.date.available","2022-09-01T09:51:17Z"],["dc.date.issued","2022"],["dc.identifier.doi","10.3892/ijo.2022.5392"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/113925"],["dc.notes.intern","DOI-Import GROB-597"],["dc.relation.eissn","1791-2423"],["dc.relation.issn","1019-6439"],["dc.title","Tumor suppressive functions of WNT5A in rhabdomyosarcoma"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","67"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Cellular and Molecular Gastroenterology and Hepatology"],["dc.bibliographiccitation.lastpage","82.e1"],["dc.bibliographiccitation.volume","5"],["dc.contributor.author","Westendorp, B. Florien"],["dc.contributor.author","Büller, Nikè V.J.A."],["dc.contributor.author","Karpus, Olga N."],["dc.contributor.author","van Dop, Willemijn A."],["dc.contributor.author","Koster, Jan"],["dc.contributor.author","Versteeg, Rogier"],["dc.contributor.author","Koelink, Pim J."],["dc.contributor.author","Snel, Clinton Y."],["dc.contributor.author","Meisner, Sander"],["dc.contributor.author","Roelofs, Joris J.T.H."],["dc.contributor.author","Uhmann, Anja"],["dc.contributor.author","Ver Loren van Themaat, Emiel"],["dc.contributor.author","Heijmans, Jarom"],["dc.contributor.author","Hahn, Heidi"],["dc.contributor.author","Muncan, Vanesa"],["dc.contributor.author","Wildenberg, Manon E."],["dc.contributor.author","van den Brink, Gijs R."],["dc.date.accessioned","2020-12-10T14:25:00Z"],["dc.date.available","2020-12-10T14:25:00Z"],["dc.date.issued","2018"],["dc.identifier.doi","10.1016/j.jcmgh.2017.08.004"],["dc.identifier.issn","2352-345X"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/72406"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Indian Hedgehog Suppresses a Stromal Cell–Driven Intestinal Immune Response"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1556"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","Journal of Investigative Dermatology"],["dc.bibliographiccitation.lastpage","1565.e11"],["dc.bibliographiccitation.volume","140"],["dc.contributor.author","Becker, Marco"],["dc.contributor.author","Bauer, Julia"],["dc.contributor.author","Pyczek, Joanna"],["dc.contributor.author","König, Simone"],["dc.contributor.author","Müllen, Anna"],["dc.contributor.author","Rabe, Hanna"],["dc.contributor.author","Schön, Michael P."],["dc.contributor.author","Uhmann, Anja"],["dc.contributor.author","Hahn, Heidi"],["dc.date.accessioned","2021-04-14T08:24:35Z"],["dc.date.available","2021-04-14T08:24:35Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.1016/j.jid.2019.11.030"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/81343"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation.issn","0022-202X"],["dc.title","WIF1 Suppresses the Generation of Suprabasal Cells in Acanthotic Skin and Growth of Basal Cell Carcinomas upon Forced Overexpression"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["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"]]