Radzun, Heinz-Joachim

[["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","384"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","Archives of Dermatological Research"],["dc.bibliographiccitation.lastpage","390"],["dc.bibliographiccitation.volume","292"],["dc.contributor.author","Fayyazi, Afshin"],["dc.contributor.author","Schweyer, Stefan"],["dc.contributor.author","Eichmeyer, B."],["dc.contributor.author","Herms, J."],["dc.contributor.author","Hemmerlein, Bernhard"],["dc.contributor.author","Radzun, H.-J."],["dc.contributor.author","Berger, H."],["dc.date.accessioned","2018-11-07T10:34:41Z"],["dc.date.available","2018-11-07T10:34:41Z"],["dc.date.issued","2000"],["dc.description.abstract","Granuloma annulare, a prototype noninfectious granulomatous dermatitis, is morphologically characterized by a necrobiotic core surrounded by a cellular infiltrate, Because of many morphological similarities to tuberculosis, granuloma annulare has been suggested to represent a delayed-type hypersensitivity (Th1) reaction in the course of which inflammatory cells elicit matrix degradation, In the present study we (1) investigated the expression of interferon-gamma as the most important Th1-associated cytokine, (2) sought in situ evidence for the coexpression of the proinflammatory cytokine tumor necrosis factor-a and cytokine-regulated matrix metalloproteinases 2 (gelatinase A) and 9 (gelatinase B), and (3) sought to determine whether shrunken cells seen within necrobiotic areas of granuloma annulare are apoptotic cells, In situ hybridization combined with immunofluorescence showed that large numbers of infiltrating CD3(+) lymphocytes express interferon-gamma, Application of catalyzed signal amplification in immunodetection revealed that the vast majority of CD3(+) lymphocytes and CD68(+) macrophages contained tumor necrosis factor-alpha. Immunohistochemistry demonstrated that macrophages producing tumor necrosis factor-ct coexpress matrix metalloproteinases 2 and 9, In situ end-labeling combined with immunofluorescence detected few apoptotic T cells in perivascular regions and numerous apoptotic macrophages within necrobiotic areas, These results suggest that in granuloma annulare interferon-gamma(+) Th-1 lymphocytes may cause a delayed-type hypersensitivity reaction whereby macrophages are differentiated to aggressive effector cells expressing tumor necrosis factor-alpha and matrix metalloproteinases, In parallel, activation-induced apoptosis in lymphocytes and macrophages may serve to restrict the destructive potential of the inflammatory cells."],["dc.identifier.doi","10.1007/s004030000150"],["dc.identifier.isi","000088939700003"],["dc.identifier.pmid","10994772"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/44932"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.issn","0340-3696"],["dc.title","Expression of IFN gamma, coexpression of TNF alpha and matrix metalloproteinases and apoptosis of T lymphocytes and macrophages in granuloma annulare"],["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.firstpage","317"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Pathology - Research and Practice"],["dc.bibliographiccitation.lastpage","318"],["dc.bibliographiccitation.volume","203"],["dc.contributor.author","Schweyer, Stefan"],["dc.contributor.author","Jaenisch, S."],["dc.contributor.author","Baumhoer, D."],["dc.contributor.author","Fayyazi, Afshin"],["dc.contributor.author","Radzun, H.-J."],["dc.date.accessioned","2018-11-07T11:07:22Z"],["dc.date.available","2018-11-07T11:07:22Z"],["dc.date.issued","2007"],["dc.identifier.isi","000247312300164"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/52540"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Gmbh, Urban & Fischer Verlag"],["dc.publisher.place","Jena"],["dc.relation.issn","0344-0338"],["dc.title","Expression of CXCR3 in malignant testicular germ cell tumours"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","589"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","British Journal of Cancer"],["dc.bibliographiccitation.lastpage","598"],["dc.bibliographiccitation.volume","91"],["dc.contributor.author","Schweyer, Stefan"],["dc.contributor.author","Soruri, Afsaneh"],["dc.contributor.author","Meschter, O."],["dc.contributor.author","Heintze, A."],["dc.contributor.author","Zschunke, F."],["dc.contributor.author","Miosge, Nicolai"],["dc.contributor.author","Thelen, Paul"],["dc.contributor.author","Schlott, T."],["dc.contributor.author","Radzun, H.-J."],["dc.contributor.author","Fayyazi, Afshin"],["dc.date.accessioned","2018-11-07T10:46:28Z"],["dc.date.available","2018-11-07T10:46:28Z"],["dc.date.issued","2004"],["dc.description.abstract","Testicular germ cell tumours (TGCT) represent the most common malignancies in young males. Whereas in 1970s, the survival rate in patients with metastatic testicular tumours was only 5%, these days, 80% of the patients treated by modern chemotherapy will survive their disease. The drug that revolutionised the cure rate for patients with metastatic testicular tumours was cisdiamminedichloroplatinum ( cisplatin, CDDP). In vitro experiments on neoplastic germ cell lines showed that their exquisite sensitivity to CDDP could be attributed to p53-dependent and -independent pathways. Applying cDNA macroarray, semiquantitative RT-PCR and Western blot analyses, blocking experiments, caspase activity assays, and morphological methods, we sought here to define the p53-independent pathway(s) involved in the CDDP-induced apoptosis. For this purpose, we used the human TGCT cell line NCCIT, the mutated p53 of which is known to remain inactive during the course of CDDP-induced apoptosis. Our experiments showed that within hours of CDDP application, two prototype members of the 'mitogen-activated protein kinase' ( MAPK) family, designated 'MAPK ERK kinase' (MEK) and 'extracellular signal-regulated kinase' ( ERK), were dually phosphorylated and caspase-3 became active. Functional assays using MEK inhibitors demonstrated that the phosphorylation of MEK and ERK was required for the activation of caspase-3 as the executing caspase. Interestingly, experiments with the human malignant germ cell line NTERA, which is known to possess wild-type p53, revealed the same results. Thus, our data suggest that CDDP mediates its p53-independent apoptosis-inducing effect on the malignant human testicular germ cells - at least partially - through activation of the MEK - ERK signalling pathway."],["dc.identifier.doi","10.1038/sj.bjc.6601919"],["dc.identifier.isi","000222930400029"],["dc.identifier.pmid","15266324"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/47752"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","0007-0920"],["dc.title","Cisplatin-induced apoptosis in human malignant testicular germ cell lines depends on MEK/ERK activation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","976"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","Apmis"],["dc.bibliographiccitation.lastpage","981"],["dc.bibliographiccitation.volume","121"],["dc.contributor.author","Bremmer, Felix"],["dc.contributor.author","Schweyer, Stefan"],["dc.contributor.author","Martin-Ortega, M."],["dc.contributor.author","Hemmerlein, Bernhard"],["dc.contributor.author","Strauss, A."],["dc.contributor.author","Radzun, H.-J."],["dc.contributor.author","Behnes, Carl Ludwig"],["dc.date.accessioned","2018-11-07T09:19:27Z"],["dc.date.available","2018-11-07T09:19:27Z"],["dc.date.issued","2013"],["dc.description.abstract","Leydig cell tumours comprise about 3% of all testicular tumours. The pathogenesis of Leydig cell tumours is still poorly understood. We investigated testis with Leydig cell hyperplasia and Leydig cell tumours for their expression pattern of P- and N-cadherin. We could show a switch of expression of P- and N-cadherin in Leydig cell hyperplasia and Leydig cell tumours in comparison with normal Leydig cells. Cadherins could be established as a new immunohistochemical marker for this testicular tumour entity; their possible role in tumour genesis will be discussed."],["dc.identifier.doi","10.1111/apm.12053"],["dc.identifier.isi","000325026100009"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/28638"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","0903-4641"],["dc.title","Switch of cadherin expression as a diagnostic tool for Leydig cell tumours"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","915"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","British Journal of Cancer"],["dc.bibliographiccitation.lastpage","921"],["dc.bibliographiccitation.volume","89"],["dc.contributor.author","Schweyer, Stefan"],["dc.contributor.author","Soruri, Afsaneh"],["dc.contributor.author","Peters, J."],["dc.contributor.author","Wagner, A."],["dc.contributor.author","Radzun, H.-J."],["dc.contributor.author","Fayyazi, Afshin"],["dc.date.accessioned","2018-11-07T10:36:22Z"],["dc.date.available","2018-11-07T10:36:22Z"],["dc.date.issued","2003"],["dc.description.abstract","Cytokines possess discrepant effects on tumour cells varying from anti- to proapoptotic activities. We recently reported that testicular germ cell tumours (TGCT) express a functional form of the proinflammatory cytokine interferon-gamma (IFNgamma). The present study asked whether TGCT-derived IFNgamma influences survival or death of neoplastic germ cells. Analysis of TGCT cell lines demonstrated that they expressed and secreted IFNgamma, but were resistant to the endogenous IFNgamma since neutralisation of IFNgamma by a specific blocking antibody had no influence on the proliferation and/or the degree of apoptosis of tumour cells. To study mechanisms providing tumour resistance to endogenous IFNgamma, we analysed primary TGCT and two human TGCT cell lines (NTERA and NCCIT) for the expression of IFNgamma receptor and for the level of phosphorylation of the signal transducer and activator of transcription ( STAT)-1. In situ hybridisation, immunocytochemistry, Western blot analysis and flow cytometry indicated that primary TGCT as well as NCCIT and NTERA cell lines expressed the heterodimeric cell surface IFNg receptor which consists of both 90-kDa alpha- and the 85-kDa beta-chains. However, the downstream transcription factor STAT-1 was not phosphorylated constitutively, indicating that STAT-1 is not activated by the endogenous IFNgamma. Upon application of recombinant human IFNgamma in excess, however, STAT-1 was phosphorylated and the interferon regulatory factor-1 (IRF-1) was induced, suggesting that both IFNgammaR and STAT-1 are functionally intact in TGCT. Altogether our results suggest that despite secreting biologically active IFNgamma, the concentration of the endogenous IFNgamma is too low to stimulate the IFNgammaR/STAT signalling pathway in TGCT in an autocrine and/or paracrine manner."],["dc.identifier.doi","10.1038/sj.bjc.6601209"],["dc.identifier.isi","000185074900023"],["dc.identifier.pmid","12942126"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/45305"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","0007-0920"],["dc.title","Malignant germ cell tumours of the testis express interferon-gamma, but are resistant to endogenous interferon-gamma"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","222"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Immunology"],["dc.bibliographiccitation.lastpage","230"],["dc.bibliographiccitation.volume","105"],["dc.contributor.author","Soruri, Afsaneh"],["dc.contributor.author","Schweyer, Stefan"],["dc.contributor.author","Radzun, H.-J."],["dc.contributor.author","Fayyazi, Afshin"],["dc.date.accessioned","2018-11-07T10:32:12Z"],["dc.date.available","2018-11-07T10:32:12Z"],["dc.date.issued","2002"],["dc.description.abstract","The morbidity and lethality of tuberculosis is partially the result of an ineffective delayed-type hypersensitivity reaction which causes caseating granulomas in the lung and other organs. Recently we showed that during caseation besides macrophages numerous Fas(+) FasL(+) lymphocytes undergo apoptosis and postulated that this phenomenon may be due to activation-induced cell death (AICD) as a consequence of T-lymphocyte reactivation via bacillary antigens. As purified protein derivative of Mycobacterium tuberculosis (Mtb-PPD) provokes caseation in tuberculosis patients, the question arose as to whether bacillary antigens are responsible for AICD within caseous areas. In the present study Mtb-PPD-specific T helper 1 (Th1)-differentiated T lymphocytes were generated in vitro, Reactivation of these cells with Mtb-PPD resulted in a concentration-dependent hyporesponsiveness, which was due to an increase in apoptosis of gammadelta(+), alphabeta(+) CD4(+) as well as alphabeta(+) CD8(+) T lymphocytes as assessed by the demonstration of the apoptosis-associated mitochondrial membrane protein 7A6 and DNA fragmentation. Blocking experiments demonstrated that Mtb-PPD antigens exploited the Fas/FasL system to induce apoptosis in Mtb-PPD-specific T lymphocytes. These results may support the hypothesis that in tubercle granulomas with caseation T lymphocytes undergo AICD following reactivation by bacillary antigens, thus contributing to the persistence of tuberculosis."],["dc.identifier.doi","10.1046/j.0019-2805.2001.01355.x"],["dc.identifier.isi","000173866100013"],["dc.identifier.pmid","11872098"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/44290"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Blackwell Publishing Ltd"],["dc.relation.issn","0019-2805"],["dc.title","Mycobacterial antigens induce apoptosis in human purified protein derivative-specific up T lymphocytes in a concentration-dependent manner"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","255"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Gut"],["dc.bibliographiccitation.lastpage","259"],["dc.bibliographiccitation.volume","46"],["dc.contributor.author","Schweyer, Stefan"],["dc.contributor.author","Mihm, Sabine"],["dc.contributor.author","Radzun, H.-J."],["dc.contributor.author","Hartmann, Hans"],["dc.contributor.author","Fayyazi, Afshin"],["dc.date.accessioned","2018-11-07T10:25:22Z"],["dc.date.available","2018-11-07T10:25:22Z"],["dc.date.issued","2000"],["dc.description.abstract","Background-Pathogenesis of hepatitis C virus (HCV) associated Liver injury is thought to be due to the host antiviral immune response. Using a quantitative, competitive RT-PCR technique, we recently showed that expression of interferon gamma (IFN-gamma) and IFN-gamma inducible type of nitric oxide synthase (iNOS) is increased in homogenised liver tissue of patients with chronic HCV infection. Aims--To determine the cellular origin of IFN-gamma and iNOS expression and to examine the hypothesis that T cell derived IFN-gamma secretion induces iNOS in hepatocytes in chronic HCV infection. Methods--By applying a non-radioactive in situ hybridisation method combined with indirect immunofluorescence, 33 liver biopsy specimens from patients with chronic HCV infection were studied for cellular expression of IFN-gamma and iNOS mRNA. Results--In chronic HCV infection, both IFN-gamma and iNOS gene expression were significantly increased. IFN-gamma and iNOS mRNA were observed in CD3+ lymphocytes infiltrating portal tracts and hepatic lobules, but not in hepatocytes. Conclusions-Results are consistent with previous reports that IFN-gamma and iNOS transcripts are elevated in chronic HCV infection. In contrast to the hypothesis, IFN-gamma expressing T cells do not induce iNOS in hepatocytes, but probably in T cells. T lymphocytes expressing IFN-gamma and/or iNOS have the potential to participate in autocrine and paracrine pathways that may contribute to the pathobiology of chronic hepatitis C."],["dc.identifier.doi","10.1136/gut.46.2.255"],["dc.identifier.isi","000084976700023"],["dc.identifier.pmid","10644322"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/42847"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","British Med Journal Publ Group"],["dc.relation.issn","0017-5749"],["dc.title","Liver infiltrating T lymphocytes express interferon gamma and inducible nitric oxide synthase in chronic hepatitis C virus infection"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","201"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Human Molecular Genetics"],["dc.bibliographiccitation.lastpage","211"],["dc.bibliographiccitation.volume","15"],["dc.contributor.author","Lee, J. H."],["dc.contributor.author","Schutte, D."],["dc.contributor.author","Wulf, Gerald"],["dc.contributor.author","Fuzesi, Laszlo"],["dc.contributor.author","Radzun, H.-J."],["dc.contributor.author","Schweyer, Stefan"],["dc.contributor.author","Engel, Wolfgang"],["dc.contributor.author","Nayernia, K."],["dc.date.accessioned","2018-11-07T10:26:33Z"],["dc.date.available","2018-11-07T10:26:33Z"],["dc.date.issued","2006"],["dc.description.abstract","The genes of the piwi family are defined by conserved PAZ and Piwi domains and play important roles in stem-cell self-renewal, RNA silencing and translational regulation in various organisms. Both, mouse and human Piwil2 genes, members of the piwi gene family, are specifically expressed in testis. We report here enhanced expression of the human Piwil2 gene in testicular seminomas, but not in testicular non-seminomatous tumors. Expression of the Piwil2 gene was also found in different tumors examined, including prostate, breast, gastrointestinal, ovarian and endometrial cancer of human and in breast tumors, rhabdomyosarcoma and medulloblastoma of mouse. Therefore, Piwil2 can be categorized as a novel member of cancer/testis antigens. To identify genes activated by Piwil2, RNA isolated from NIH-3T3 cells expressing constitutively Piwil2 were compared with RNA samples from control NIH-3T3 cells using a cancer gene array. Induction of high-level expression of the antiapoptotic gene Bcl-X-L was observed in cells expressing Piwil2. Furthermore, increased Bcl-X-L expression correlated with increase of signal transducer and activator of transcription 3 (Stat3) expression. Gene silencing of Piwil2 with its small interference RNA suppressed Stat3 and Bcl-X-L expression and induced apoptosis. A causal link between Piwil2 expression and inhibition of apoptosis and enhanced proliferation was demonstrated in cells expressing Piwil2. Furthermore, results of soft agar assay indicated that Piwil2 overexpression induced transformation of fibroblast cells. In summary, our results demonstrate that Piwil2 is widely expressed in tumors and acts as an oncogene by inhibition of apoptosis and promotion of proliferation via Stat3/Bcl-X-L signaling pathway. Expression of Piwil2 in a wide variety of tumors could be a useful prognostic factor that could have also diagnostic and therapeutic implications."],["dc.identifier.doi","10.1093/hmg/ddi430"],["dc.identifier.isi","000234630400003"],["dc.identifier.pmid","16377660"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/43069"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Oxford Univ Press"],["dc.relation.issn","0964-6906"],["dc.title","Stem-cell protein Piwil2 is widely expressed in tumors and inhibits apoptosis through activation of Stat3/Bcl-X-L pathway"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]