Thelen, Paul

[["dc.bibliographiccitation.firstpage","341"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Anticancer Research"],["dc.bibliographiccitation.lastpage","349"],["dc.bibliographiccitation.volume","32"],["dc.contributor.author","Bremmer, Felix"],["dc.contributor.author","Thelen, Paul"],["dc.contributor.author","Pottek, T."],["dc.contributor.author","Behnes, Carl Ludwig"],["dc.contributor.author","Radzun, H.-J."],["dc.contributor.author","Schweyer, Stefan"],["dc.date.accessioned","2018-11-07T09:16:04Z"],["dc.date.available","2018-11-07T09:16:04Z"],["dc.date.issued","2012"],["dc.description.abstract","Testicular germ cell tumours (TGCTs) are the most common malignancy in young men aged 18-35 years. They are clinically and histologically subdivided into seminomas and non-seminomas. 1,25-Dihydroxyvitamin,25(OH)(2)D(3)) is the active form of vitamin D and exerts its actions via a specific intracellular vitamin D receptor (VDR). Several investigations in the recent years have revealed, in addition to a physiological occurrence of the VDR in various tissues, VDR expression in different human malignancies. Furthermore, 1,25(OH)(2)D(3) plays an important role in the regulation of cell proliferation and differentiation. In different normal and malignant cell types, antiproliferative and pro-differentiating effects of 1,25(OH)(2)D(3) are described. We investigated whether TGCT express the VDR, wether differences exist between the histological subtypes and if vitamin D has a function on the proliferation of tumour cells. Furthermore, we investigated the potential function of the vitamin D-regulated genes nuclear receptor co-repressor 1 (NCOR1), nuclear receptor co-repressor 2 (NCOR2), thyroid receptor interacting protein 15 (TRIP I 5), Growth Arrest and DNA Damage (GADD45), MAP kinase-activated protein kinase 2 (MAPKAPK2), Cytochmme P450, family 24, subfamily A, polypeptide 1 (C.YP24A1) and Cytochrome P450, family 27, subfamily B. polypeptide (CYP27B1) in the pathogenesis of TGCT. We demonstrate, for the first time, that primary TGCT as well as TGCT cell lines, express VDR mRNA and protein. Vitamin D and VDR may play a role in the pathogenesis of TGCTs. Furthermore, vitamin D inhibits proliferation of TGCT cell-lines, potentially via an increase in expression of GADD45. Our data suggest that vitamin D could play a role in antitumour therapy."],["dc.identifier.isi","000298780700017"],["dc.identifier.pmid","22213325"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/27850"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Int Inst Anticancer Research"],["dc.relation.issn","0250-7005"],["dc.title","Expression and Function of the Vitamin D Receptor in Malignant Germ Cell Tumour of the Testis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","339"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","International Journal of Molecular Medicine"],["dc.bibliographiccitation.lastpage","346"],["dc.bibliographiccitation.volume","31"],["dc.contributor.author","Thelen, Paul"],["dc.contributor.author","Krahn, Lisa"],["dc.contributor.author","Bremmer, Felix"],["dc.contributor.author","Strauss, Arne"],["dc.contributor.author","Brehm, Ralph"],["dc.contributor.author","Loertzer, Hagen"],["dc.date.accessioned","2018-11-07T09:28:47Z"],["dc.date.available","2018-11-07T09:28:47Z"],["dc.date.issued","2013"],["dc.description.abstract","The aim of this study was to elucidate whether the treatment of a prostate carcinoma cell line (LNCaP) and LNCaP-derived tumors with the histone deacetylase (HDAC) inhibitor valproate in combination with the mammalian target of rapamycin (mTOR) inhibitor temsirolimus resulted in synergistic effects on cell proliferation and tumor growth. LNCaP cells were treated with valproate, temsirolimus or a combination of both. The proliferation rates and the expression of key markers of tumorigenesis were evaluated. In in vivo experiments, LNCaP cells were implanted into immune-suppressed male nude mice. Mice were treated with valproate (per os), temsirolimus (intravenously) or with a combination of both. Tumor volumes were calculated and mRNA expression was quantified. The incubation of LNCaP cells with the combination of valproate and temsirolimus resulted in a decrease of cell proliferation with an additive effect of both drugs in comparison to the single treatment. In particular, the combined application of valproate and temsirolimus led to a significant upregulation of insulin-like growth factor-binding protein-3 (IGFBP-3), which mediates apoptosis and inhibits tumor cell proliferation. In the mouse model, we found no significant differences in tumor growth between the different treatment arms but immunohistological analyses showed that tumors treated with a combination of valproate and temsirolimus, but not with the single drugs alone, exhibited a significant lower proliferation capacity."],["dc.identifier.doi","10.3892/ijmm.2012.1221"],["dc.identifier.isi","000313858500009"],["dc.identifier.pmid","23292124"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/30859"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Spandidos Publ Ltd"],["dc.relation.issn","1107-3756"],["dc.title","Synergistic effects of histone deacetylase inhibitor in combination with mTOR inhibitor in the treatment of prostate carcinoma"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","72"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","The Journal of Pathology"],["dc.bibliographiccitation.lastpage","81"],["dc.bibliographiccitation.volume","213"],["dc.contributor.author","Schweyer, Stefan"],["dc.contributor.author","Bachem, A."],["dc.contributor.author","Bremmer, Felix"],["dc.contributor.author","Steinfelder, Hans Juergen"],["dc.contributor.author","Soruri, Afsaneh"],["dc.contributor.author","Wagner, W."],["dc.contributor.author","Pottek, T."],["dc.contributor.author","Thelen, Paul"],["dc.contributor.author","Hopker, W. W."],["dc.contributor.author","Radzun, H.-J."],["dc.contributor.author","Fayyazi, Afshin"],["dc.date.accessioned","2018-11-07T10:59:10Z"],["dc.date.available","2018-11-07T10:59:10Z"],["dc.date.issued","2007"],["dc.description.abstract","Testicular germ cell tumours (TGCT) represent the most common malignancy in young males. We reported previously that two prototype members of the mitogen-activated protein kinase (MAPK) family, the MAPK ERK kinase (MEK) and extracellular signal-regulated kinase (ERK), are inactive in malignant testicular germ cells and become active after drug stimulation, leading to apoptosis of tumour cells. In this study, we asked whether the protein phosphatase PP2A, a known inhibitor of the MEK-ERK pathway, participates in the proliferation and/or apoptosis of primary TGCT (n = 48) as well as two TGCT cell lines (NTERA and NCCIT). Quantitative RT-PCR, immunohistochemistry, western blot analyses and phosphatase assay indicate that primary TGCT as well as TGCT cell lines express PP2A and that PP2A is active in TGCT cell lines. The inhibition of PP2A by application of two PP2A inhibitors, cantharidic acid (CA) and okadaic acid (OA), results in a significant increase in caspase-3-mediated apoptosis of TGCT cell lines. Thereby, PP2A inhibition was accompanied by phosphorylation and activation of MEK and ERK. Functional assays using the MEK inhibitor PD98059 demonstrated that the phosphorylation of NIEK and ERK was required for the induction of caspase-3-mediated apoptosis of malignant germ cells. Thus, our data suggest that inhibition of PP2A mediates its apoptosis-inducing effect on TGCT through activation of the MEK-ERK signalling pathway that leads to caspase-3-mediated apoptosis of tumour cells. In addition our results support previous observations that PP2A exerts an anti-apoptotic effect on malignant tumour cells. Copyright (c) 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd."],["dc.identifier.doi","10.1002/path.2203"],["dc.identifier.isi","000249181800009"],["dc.identifier.pmid","17590861"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/50636"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","John Wiley & Sons Ltd"],["dc.relation.issn","0022-3417"],["dc.title","Expression and function of protein phosphatase PP2A in malignant testicular germ cell tumours"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Journal of Clinical Oncology"],["dc.bibliographiccitation.volume","31"],["dc.contributor.author","Thelen, Paul"],["dc.contributor.author","Walleck, Eiko"],["dc.contributor.author","Bremmer, Felix"],["dc.contributor.author","Trojan, Lutz"],["dc.contributor.author","Strauss, Arne"],["dc.date.accessioned","2018-11-07T09:28:04Z"],["dc.date.available","2018-11-07T09:28:04Z"],["dc.date.issued","2013"],["dc.identifier.isi","000333679600131"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/30688"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Soc Clinical Oncology"],["dc.publisher.place","Alexandria"],["dc.relation.conference","Genitourinary Cancers Symposium of the Conquer-Cancer-Foundation of American-Society-of-Clinical-Oncology (ASCO)"],["dc.relation.eventlocation","Orlando, FL"],["dc.relation.issn","1527-7755"],["dc.relation.issn","0732-183X"],["dc.title","Analysis of putative resistance mechanisms in recent treatments targeting the androgen receptor in castration-resistant prostate cancer (CRPC)"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","574"],["dc.bibliographiccitation.journal","SpringerPlus"],["dc.bibliographiccitation.volume","3"],["dc.contributor.author","Bremmer, Felix"],["dc.contributor.author","Jarry, Hubertus"],["dc.contributor.author","Strauss, Arne"],["dc.contributor.author","Behnes, Carl Ludwig"],["dc.contributor.author","Trojan, Lutz"],["dc.contributor.author","Thelen, Paul"],["dc.date.accessioned","2018-11-07T09:33:49Z"],["dc.date.available","2018-11-07T09:33:49Z"],["dc.date.issued","2014"],["dc.description.abstract","Recent breakthrough therapies targeting androgen receptor signalling in castration resistant prostate cancer (CRPC) involve multifunctional androgen receptor (AR) blockade and exhaustive androgen deprivation. Nevertheless, limitations to an enduring effectiveness of new drugs are anticipated in resistance mechanisms occurring under such treatments. In this study we used CRPC cell models VCaP and LNCaP as well as AR-negative PC-3- and non-neoplastic epithelial BPH-1-cells treated with 5, 10 or 25 mu mol/L abiraterone hydrolyzed from abiraterone acetate (AA). The origin of CYP17A1 up-regulation under AA treatment was investigated in CRPC cell models by qRT-PCR and western-blot procedures. AA treatments of AR positive CRPC cell models led to decreased expression of androgen regulated genes such as PSA. In these cells diminished expression of androgen regulated genes was accompanied by an up-regulation of CYP17A1 expression within short-term treatments. No such effects became evident in AR-negative PC-3 cells. AR directed siRNA (siAR) used in VCaP cells significantly reduced mRNA expression and AR protein abundance. Such interference with AR signalling in the absence of abiraterone acetate also caused a marked up-regulation of CYP17A1 expression. Down-regulation of androgen regulated genes occurs in spite of an elevated expression of CYP17A1, the very target enzyme for this drug. CYP17A1 up-regulation already takes place within such short treatments with AA and does not require adaptation events over several cell cycles. CYP17A1 is also up-regulated in the absence of AA when AR signalling is physically eliminated by siAR. These results reveal an immediate counter-regulation of CYP17A1 expression whenever AR-signalling is inhibited adequately but not a persisting adaptation yielding drug resistance."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft (DFG)"],["dc.identifier.doi","10.1186/2193-1801-3-574"],["dc.identifier.isi","000359105300002"],["dc.identifier.pmid","25332874"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/11151"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/32049"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.issn","2193-1801"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Increased expression of CYP17A1 indicates an effective targeting of the androgen receptor axis in castration resistant prostate cancer (CRPC)"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Journal of Clinical Oncology"],["dc.bibliographiccitation.volume","32"],["dc.contributor.author","Thelen, Paul"],["dc.contributor.author","Jarry, Hubertus"],["dc.contributor.author","Trojan, Lutz"],["dc.contributor.author","Brookman-May, Sabine"],["dc.contributor.author","Bremmer, Felix"],["dc.date.accessioned","2018-11-07T09:43:56Z"],["dc.date.available","2018-11-07T09:43:56Z"],["dc.date.issued","2014"],["dc.identifier.isi","000335318100157"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/34286"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Soc Clinical Oncology"],["dc.publisher.place","Alexandria"],["dc.relation.conference","Genitourinary Cancers Symposium"],["dc.relation.eventlocation","San Francisco, CA"],["dc.relation.issn","1527-7755"],["dc.relation.issn","0732-183X"],["dc.title","In vitro reproduction and explanation of an abiraterone acetate withdrawal phenomenon."],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","66"],["dc.bibliographiccitation.journal","EJNMMI Research"],["dc.bibliographiccitation.volume","5"],["dc.contributor.author","Meller, Birgit"],["dc.contributor.author","Bremmer, Felix"],["dc.contributor.author","Sahlmann, Carsten-Oliver"],["dc.contributor.author","Hijazi, Sameh"],["dc.contributor.author","Bouter, Caroline"],["dc.contributor.author","Trojan, Lutz"],["dc.contributor.author","Meller, J."],["dc.contributor.author","Thelen, Paul"],["dc.date.accessioned","2018-11-07T09:48:52Z"],["dc.date.available","2018-11-07T09:48:52Z"],["dc.date.issued","2015"],["dc.description.abstract","Background: Prostate-specific membrane antigen (PSMA) is a promising target for diagnostics and therapy of prostate carcinoma (PCa). Based on the hypothesis that PSMA expression can be modulated by variations in androgen deprivation therapy (ADT), we investigated the binding of a PSMA-directed radiopharmaceutical in vitro in order to get an insight of the interactions between altered premedication and PSMA expression before repetitive PSMA-directed PET/CT for therapy response and targeted therapy implementation. Methods: The human castration-resistant PCa cell line VCaP (CRPC) was treated with either 1 nmol/L testosterone (T) over 20 passages yielding the androgen-sensitive cell line (revCRPC) or with 5 mu mol/L abiraterone acetate (AA) generating the abiraterone-tolerant subtype CRPCAA. In these cell lines, T and AA were varied by either supply or withdrawal of T and AA. PSMA expression of the three cell culture models was detected by Western blot and immunohistochemical staining. For quantitative measurement of tracer uptake, 0.3 nmol/L Ga-68-labelled PSMA-HBED-CC peptide (100-300 kBq/ml) was added to different treated parallel cultures (n = 9 each). Time-dependent uptake per 10(6) cells of each culture was calculated and evaluated. PSMA mRNA expression was investigated by qPCR. Results: PSMA expression increased dependently on intensified ADT in all three basic cell lines. Ga-68-PSMA-HBED-CC uptake almost doubled during 3 h in all cell lines (p < 0.01). Compared to the basic cells, pre-incubation with abiraterone for 48 h resulted in a significant increased uptake in CRPC (p < 0.001). In revCRPC, 48-h AA pre-incubation resulted in an eightfold higher uptake after 3 h (p < 0.001). Additional withdrawal of external testosterone increased the uptake up to tenfold (p < 0.01). The increase of PSMA expression upon ADT and AA treatments was confirmed by qPCR and Western blot data. Furthermore, in CRPCAA, 48-h AA withdrawal increased the uptake up to fivefold (p < 0.01). Conclusions: The investigated three PCa cell culture subtypes represent a serial preclinical model of androgen deprivation therapy as a proxy for clinical situations with differing basal PSMA expression. The uptake of PSMA-binding tracers could be stimulated by therapeutic effective short-term variation in premedication in all stages of ADT response. These complex interactions have to be considered in the interpretation of diagnostic imaging using PSMA ligands as well as in the optimal timing of PSMA-based therapies."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft DFG [TH 389/3-1, BR4700/1-1]"],["dc.identifier.doi","10.1186/s13550-015-0145-8"],["dc.identifier.isi","000364963600001"],["dc.identifier.pmid","26576996"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/12584"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/35393"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.publisher.place","Heidelberg"],["dc.relation.issn","2191-219X"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Alterations in androgen deprivation enhanced prostate-specific membrane antigen (PSMA) expression in prostate cancer cells as a target for diagnostics and therapy"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","34971"],["dc.bibliographiccitation.issue","21"],["dc.bibliographiccitation.journal","Oncotarget"],["dc.bibliographiccitation.lastpage","34979"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Gehrig, Julia"],["dc.contributor.author","Kaulfuss, Silke"],["dc.contributor.author","Jarry, Hubertus"],["dc.contributor.author","Bremmer, Felix"],["dc.contributor.author","Stettner, Mark"],["dc.contributor.author","Burfeind, Peter"],["dc.contributor.author","Thelen, Paul"],["dc.date.accessioned","2018-11-07T10:23:41Z"],["dc.date.available","2018-11-07T10:23:41Z"],["dc.date.issued","2017"],["dc.description.abstract","Advanced prostate cancer can develop into castration-resistant prostate cancer (CRPC). This process is mediated either by intratumoral ligand synthesis or by mutations or aberrations of the androgen receptor (AR) or its cofactors. To date, no curative therapy for CRPC is available, as AR-targeted therapies eventually result in the development of resistance. The human prostate cancer cell line VCaP (vertebral cancer of the prostate) overexpresses AR and its splice variants (ARVs) as a mechanism of resistance to androgen-deprivation therapy (ADT) of external and intratumoral origin. In the present study, we demonstrate that stimulating estrogen receptor beta activity with the specific agonist 8 beta-VE2 in VCaP cells in successive stages of ADT induced a time-and dose-dependent decrease in cell survival and an increase in apoptosis. Furthermore, 8 beta-VE2 treatment reduced the overexpression of the AR as well as ARVs in VCaP cells under maximum ADT. Our results indicate that decreased survival of the androgen-dependent CRPC cells employing apoptosis together with the regulative effect on AR expression could have beneficial effects over current AR-targeting therapies."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2017"],["dc.identifier.doi","10.18632/oncotarget.16496"],["dc.identifier.isi","000402051700085"],["dc.identifier.pmid","28380417"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14426"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/42509"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Impact Journals Llc"],["dc.relation.issn","1949-2553"],["dc.rights","CC BY 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/3.0"],["dc.title","Prospects of estrogen receptor beta activation in the treatment of castration-resistant prostate cancer"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","19"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","BMC Clinical Pathology"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Bremmer, Felix"],["dc.contributor.author","Hemmerlein, Bernhard"],["dc.contributor.author","Strauss, Arne"],["dc.contributor.author","Burfeind, Peter"],["dc.contributor.author","Thelen, Paul"],["dc.contributor.author","Radzun, Heinz-Joachim"],["dc.contributor.author","Behnes, Carl Ludwig"],["dc.date.accessioned","2019-07-09T11:54:07Z"],["dc.date.available","2019-07-09T11:54:07Z"],["dc.date.issued","2012"],["dc.description.abstract","Background Testicular germ cell tumours (TGCTs) are the most common malignancy in young men aged 18–35 years. They are clinically and histologically subdivided into seminomas and non-seminomas. Cadherins are calcium-dependent transmembrane proteins of the group of adhesion proteins. They play a role in the stabilization of cell-cell contacts, the embryonic morphogenesis, in the maintenance of cell polarity and signal transduction. N-cadherin (CDH2), the neuronal cadherin, stimulates cell-cell contacts during migration and invasion of cells and is able to suppress tumour cell growth. Methods Tumour tissues were acquired from 113 male patients and investigated by immunohistochemistry, as were the three TGCT cell lines NCCIT, NTERA-2 and Tcam2. A monoclonal antibody against N-cadherin was used. Results Tumour-free testis and intratubular germ cell neoplasias (unclassified) (IGCNU) strongly expressed N-cadherin within the cytoplasm. In all seminomas investigated, N-cadherin expression displayed a membrane-bound location. In addition, the teratomas and yolk sac tumours investigated also differentially expressed N-cadherin. In contrast, no N-cadherin could be detected in any of the embryonal carcinomas and chorionic carcinomas examined. This expression pattern was also seen in the investigated mixed tumours consisting of seminomas, teratomas, and embryonal carcinoma. Conclusions N-cadherin expression can be used to differentiate embryonal carcinomas and chorionic carcinomas from other histological subtypes of TGCT."],["dc.identifier.doi","10.1186/1472-6890-12-19"],["dc.identifier.fs","593171"],["dc.identifier.pmid","23066729"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/8499"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/60578"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.rights","CC BY 2.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.0"],["dc.title","N-cadherin expression in malignant germ cell tumours of the testis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1115"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Carcinogenesis"],["dc.bibliographiccitation.lastpage","1124"],["dc.bibliographiccitation.volume","34"],["dc.contributor.author","Witt, Daria"],["dc.contributor.author","Burfeind, Peter"],["dc.contributor.author","von Hardenberg, Sandra"],["dc.contributor.author","Opitz, Lennart"],["dc.contributor.author","Salinas-Riester, Gabriela"],["dc.contributor.author","Bremmer, Felix"],["dc.contributor.author","Schweyer, Stefan"],["dc.contributor.author","Thelen, Paul"],["dc.contributor.author","Neesen, Juergen"],["dc.contributor.author","Kaulfuss, Silke"],["dc.date.accessioned","2018-11-07T09:25:10Z"],["dc.date.available","2018-11-07T09:25:10Z"],["dc.date.issued","2013"],["dc.description.abstract","In this study, primary murine prostate cancer (PCa) cells were derived using the well-established TRAMP model. These PCa cells were treated with the histone deacetylase inhibitor, valproic acid (VPA), and we demonstrated that VPA treatment has an antimigrative, antiinvasive and antiproliferative effect on PCa cells. Using microarray analyses, we discovered several candidate genes that could contribute to the cellular effects we observed. In this study, we could demonstrate that VPA treatment of PCa cells causes the re-expression of cyclin D2, a known regulator that is frequently lost in PCa as we could show using immunohistochemical analyses on PCa specimens. We demonstrate that VPA specifically induces the re-expression of cyclin D2, one of the highly conserved D-type cyclin family members, in several cancer cell lines with weak or no cyclin D2 expression. Interestingly, VPA treatment had no effect in fibroblasts, which typically have high basal levels of cyclin D2 expression. The re-expression of cyclin D2 observed in PCa cells is activated by increased histone acetylation in the promoter region of the Ccnd2 gene and represents one underlying molecular mechanism of VPA treatment that inhibits the proliferation of cancer cells. Altogether, our results confirm that VPA is an anticancer therapeutic drug for the treatment of tumors with epigenetically repressed cyclin D2 expression."],["dc.identifier.doi","10.1093/carcin/bgt019"],["dc.identifier.isi","000318646000021"],["dc.identifier.pmid","23349020"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/30001"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Oxford Univ Press"],["dc.relation.issn","0143-3334"],["dc.title","Valproic acid inhibits the proliferation of cancer cells by re-expressing cyclin D2"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]