Now showing 1 - 10 of 13
  • 2003Journal Article
    [["dc.bibliographiccitation.firstpage","543"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","American Journal Of Pathology"],["dc.bibliographiccitation.lastpage","552"],["dc.bibliographiccitation.volume","163"],["dc.contributor.author","Grzmil, M."],["dc.contributor.author","Thelen, Paul"],["dc.contributor.author","Hemmerlein, Bernhard"],["dc.contributor.author","Schweyer, Stefan"],["dc.contributor.author","Voigt, S."],["dc.contributor.author","Mury, D."],["dc.contributor.author","Burfeind, Peter"],["dc.date.accessioned","2018-11-07T10:37:03Z"],["dc.date.available","2018-11-07T10:37:03Z"],["dc.date.issued","2003"],["dc.description.abstract","To analyze differential gene expression of putative prostate tumor markers we compared the expression levels of more than 400 cancer-related genes using the cDNA array technique in a set of capsule-invasive prostate tumor and matched normal prostate tissue. The overexpression. of Bax inhibitor-1 (BI-1) in prostate carcinoma and prostate cancer cell lines was confirmed by using Northern blot and Western blot analyses. Quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) on intact RNAs from 17 paired laser-captured microdissected epithelial tissue samples confirmed up-regulated BI-1 expression in 11 of 17 prostate tumors. In addition, it was demonstrated that BI-1 expression is down-regulated in stromal cells as. compared to matched normal epithelial cells of the prostate. In situ hybridization experiments on prostate sections also revealed that BI-1 expression is mainly restricted to epithelial cells. Furthermore, quantitative RT-PCR on RNAs derived from five benign prostate hyperplasia (BPH) samples showed no significant difference in BI-1 expression as compared to normal epithelial prostate tissue. To determine the function of BI-1 in vitro, human PC-3, LNCaP, and DU-145 prostate carcinoma cells were transfected with small interfering double-strand RNA (siRNA) oligonucleotides against the BI-1 gene leading to a specific down-regulation of BI-1 expression. Furthermore, transfection of PC-3, LNCaP, and DU-145 cells with BI-1 sequence-specific siRNAs caused a significant increase in spontaneous apoptosis in all cell lines. Taken together, our results indicate that the human BI-1 gene contains the potential to serve as a prostate cancer expression marker and as a potential target for developing therapeutic strategies for prostate cancer."],["dc.identifier.doi","10.1016/S0002-9440(10)63682-6"],["dc.identifier.isi","000184366400016"],["dc.identifier.pmid","12875974"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/45473"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Soc Investigative Pathology, Inc"],["dc.relation.issn","0002-9440"],["dc.title","Bax inhibitor-1 is overexpressed in prostate cancer and its specific down-regulation by RNA interference leads to cell death in human prostate carcinoma cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]
    Details DOI PMID PMC WOS
  • 2004Journal Article
    [["dc.bibliographiccitation.firstpage","1085"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","International Journal of Oncology"],["dc.bibliographiccitation.lastpage","1092"],["dc.bibliographiccitation.volume","24"],["dc.contributor.author","Thelen, Paul"],["dc.contributor.author","Burfeind, Peter"],["dc.contributor.author","Grzmil, M."],["dc.contributor.author","Voigt, S."],["dc.contributor.author","Ringert, Rolf-Hermann"],["dc.contributor.author","Hemmerlein, Bernhard"],["dc.date.accessioned","2018-11-07T10:49:16Z"],["dc.date.available","2018-11-07T10:49:16Z"],["dc.date.issued","2004"],["dc.description.abstract","Laser microdissection is a valuable tool to prepare pure cell populations from complex tissues for further analyses. Gene expression studies by real-time RT-PCR and cDNA arrays of microdissected tissues are becoming widely used methods. The integrity and quantity of prepared RNA must be proven to ensure reliable results in subsequent applications such as quantitative RT-PCR and cDNA-arrays. In the present study we used RNAlater(TM) protected prostate tissue for laser microdissection of tumor and tumor-free tissues. RNA quality and quantity was assessed using automated capillary gel electrophoresis. By using quantitative real time-RT-PCR before and after mRNA amplification the insulin-like growth factor binding protein-3 (IGFBP-3) gene expression was shown to be down-regulated in three out of five cases and DD3 was up-regulated in cancer tissues in all cases. The up-regulation of DD3 and the down-regulation of IGFBP-3 gene expression in cancer tissue were conserved after RNA amplification. A cDNA microarray also revealed an IGFBP-3 down-regulation in cancer tissue as well as several genes known to be differerentially expressed in prostate cancer. Taken together, we present a novel method for the isolation of intact RNA from laser microdissection-derived prostate cancer tissue useful for downstream applications of real-time RT-PCR and cDNA microarrays."],["dc.identifier.isi","000220779700004"],["dc.identifier.pmid","15067329"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/48389"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Professor D A Spandidos"],["dc.relation.issn","1019-6439"],["dc.title","cDNA microarray analysis with amplified RNA after isolation of intact cellular RNA from neoplastic and non-neoplastic prostate tissue separated by laser microdissections"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]
    Details PMID PMC WOS
  • 2004Journal Article
    [["dc.bibliographiccitation.firstpage","50"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","The Journal of Pathology"],["dc.bibliographiccitation.lastpage","59"],["dc.bibliographiccitation.volume","202"],["dc.contributor.author","Grzmil, M."],["dc.contributor.author","Hemmerlein, Bernhard"],["dc.contributor.author","Thelen, Paul"],["dc.contributor.author","Schweyer, Stefan"],["dc.contributor.author","Burfeind, Peter"],["dc.date.accessioned","2018-11-07T10:52:50Z"],["dc.date.available","2018-11-07T10:52:50Z"],["dc.date.issued","2004"],["dc.description.abstract","The type I insulin-like growth factor receptor (IGF-IR) is involved in tumour cell proliferation, invasion, and cancer cell survival. Several studies indicate that the IGF axis contributes to prostate cancer pathogenesis, but there is no consensus regarding the relative expression of the IGF-IR in benign and malignant prostate epithelium. In this study, endogenous IGF-IR gene expression was reduced in stably transfected PC-3 cells by employing an antisense RNA strategy which resulted in significant suppression of both PC3 cell invasion and proliferation in vitro. Furthermore, it was demonstrated that a direct correlation exists between the inhibition of IGF-IR gene expression and either up-regulation of IGF binding protein (BP)-3 or down-regulation of matrix metalloproteinase (MMP)2 expression in androgen-independent PC-3 cells. Moreover, inhibition of IGF-IR gene expression in transfected PC-3 cells leads to an enhanced rate of spontaneous apoptosis. In addition, expression analyses by quantitative RT-PCR on RNA from laser microdissected matched normal prostate and prostate tumour samples revealed that IGF-IR gene expression was up-regulated in nine of 12 prostate cancers, whereas IGFBP-3 gene expression was downregulated in all 12 prostate carcinomas analysed. These results indicate an important role for IGF-IR and IGFBP-3 in the homeostasis of prostate carcinoma cells and provide a further basis for targeting IGF-IR or IGFBP-3 gene expression in order to improve understanding of the IGF-IR-activated signalling pathways and as a potential treatment for prostate cancer. Copyright (C) 2003 John Wiley Sons, Ltd."],["dc.identifier.doi","10.1002/path.1492"],["dc.identifier.isi","000187668700007"],["dc.identifier.pmid","14694521"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/49206"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","John Wiley & Sons Ltd"],["dc.relation.issn","0022-3417"],["dc.title","Blockade of the type IIGF receptor expression in human prostate cancer cells inhibits proliferation and invasion, up-regulates lGF binding protein-3, and suppresses MMP-2 expression"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]
    Details DOI PMID PMC WOS
  • 2001Journal Article
    [["dc.bibliographiccitation.firstpage","645"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Virchows Archiv"],["dc.bibliographiccitation.lastpage","652"],["dc.bibliographiccitation.volume","439"],["dc.contributor.author","Hemmerlein, Bernhard"],["dc.contributor.author","Kugler, Alexander"],["dc.contributor.author","Özisik, Rehyan"],["dc.contributor.author","Ringert, Rolf-Hermann"],["dc.contributor.author","Radzun, Heinz-Joachim"],["dc.contributor.author","Thelen, Paul"],["dc.date.accessioned","2021-06-01T10:49:14Z"],["dc.date.available","2021-06-01T10:49:14Z"],["dc.date.issued","2001"],["dc.description.abstract","Rapidly growing tumors often develop necrosis. In the present study the expression of vascular endothelial growth factor (VEGF) was investigated and compared to microvessel density and necrosis of renal cell carcinomas. In the tumor-host interface the microvessel density was significantly increased compared to central tumor areas. Tumor necrosis was associated with a decrease of microvessel density and an increase of the VEGF protein expression within the perinecrotic rim. VEGF protein was focally upregulated in vital tumor tissue. An increase of the apoptotic rate of endothelia and vital tumor tissue in tumors with necrosis could not be detected. VEGF((121,165)) mRNA was decreased in proliferatively active carcinomas compared to less proliferative tumors. Multicellular renal cell cancer spheroids as a model of chronic hypoxia developed central apoptosis but no necrosis. VEGF was upregulated in the spheroid. Tumor microvessels expressed matrix metalloproteinase -2 and -9 and an incomplete pericyte covering in comparison to tumor-free tissue indicating immature active angiogenesis. We conclude that highly proliferative renal cell carcinomas outgrow their vascular supply and develop chronic hypoxia inducing a decrease of proliferation and an increase of VEGF expression. However, chronic hypoxia does not cause significant necrosis or apoptosis. Tumor necrosis is more likely induced by acute hypoxia due to immature microvessels. Furthermore, VEGF expression associated with concomitant tumor necrosis may help identify renal cell carcinomas susceptible to antiangiogenic therapy."],["dc.identifier.doi","10.1007/s004280100464"],["dc.identifier.isi","000172511300009"],["dc.identifier.pmid","11764385"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/86212"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.eissn","1432-2307"],["dc.relation.issn","0945-6317"],["dc.title","Vascular endothelial growth factor expression, angiogenesis, and necrosis in renal cell carcinomas"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]
    Details DOI PMID PMC WOS
  • 2005Journal Article
    [["dc.bibliographiccitation.firstpage","1360"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","Carcinogenesis"],["dc.bibliographiccitation.lastpage","1367"],["dc.bibliographiccitation.volume","26"],["dc.contributor.author","Thelen, Paul"],["dc.contributor.author","Scharf, Jens-Gerd"],["dc.contributor.author","Burfeind, Peter"],["dc.contributor.author","Hemmerlein, Bernhard"],["dc.contributor.author","Wuttke, Wolfgang"],["dc.contributor.author","Spengler, B."],["dc.contributor.author","Christoffel, V."],["dc.contributor.author","Ringert, Rolf-Hermann"],["dc.contributor.author","Seidlova-Wuttke, Dana"],["dc.date.accessioned","2018-11-07T10:56:59Z"],["dc.date.available","2018-11-07T10:56:59Z"],["dc.date.issued","2005"],["dc.description.abstract","Isoflavones have been shown to exert antiproliferative effects on cancer cells by steroid receptor signaling. In this study, we demonstrate the potential of plant constituents extracted from Belamcanda chinensis as anticancer drugs, which regulate the aberrant expression of genes relevant in proliferation, invasion, immortalization and apoptosis. LNCaP cells were treated with B.chinensis extract, tectorigenin or other isoflavones and mRNA expression was quantified by using real time RT-PCR. In addition, ELISA, TRAP assays and western blots were used to measure protein expression or activity. Male nude mice (n = 18) were injected subcutaneously with LNCaP cells and were fed with extracts from B.chinensis, and tumor development was monitored versus a control animal group (n = 18). Tectorigenin and several other phytochemicals downregulated PDEF, PSA and IGF-1 receptor mRNA expression in vitro. Furthermore, PSA secretion and IGF-1 receptor protein expression were diminished, and hTERT mRNA expression and telomerase activity decreased after tectorigenin treatments. However, TIMP-3 mRNA was upregulated on tectorigenin treatment. Growth of subcutaneous tumors in nude mice was delayed and diminished in animals fed with extracts from B.chinensis. The downregulation of PDEF, PSA, hTERT and IGF-1 receptor gene expression by tectorigenin demonstrates the antiproliferative potential of these agents. The upregulation of TIMP-3 gene expression indicates a pro-apoptotic function of the drug and a reduction of the invasiveness of tumors. The animal experiments demonstrate that B.chinensis markedly inhibited the development of tumors in vivo. Thus, these compounds may be useful for the prevention or treatment of human prostate cancer."],["dc.identifier.doi","10.1093/carcin/bgi092"],["dc.identifier.isi","000230724700006"],["dc.identifier.pmid","15845653"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/50140"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Oxford Univ Press"],["dc.relation.issn","0143-3334"],["dc.title","Tectorigenin and other phytochemicals extracted from leopard lily Belamcanda chinensis affect new and established targets for therapies in prostate cancer"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]
    Details DOI PMID PMC WOS
  • 2012Journal Article
    [["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"]]
    Details DOI PMID PMC
  • 2000Journal Article
    [["dc.bibliographiccitation.firstpage","104"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","UROLOGICAL RESEARCH"],["dc.bibliographiccitation.lastpage","109"],["dc.bibliographiccitation.volume","28"],["dc.contributor.author","Seseke, Florian"],["dc.contributor.author","Thelen, Paul"],["dc.contributor.author","Hemmerlein, Bernhard"],["dc.contributor.author","Kliese, D."],["dc.contributor.author","Zoller, G."],["dc.contributor.author","Ringert, Rolf-Hermann"],["dc.date.accessioned","2018-11-07T08:35:06Z"],["dc.date.available","2018-11-07T08:35:06Z"],["dc.date.issued","2000"],["dc.description.abstract","Partial obstruction of the upper urinary tract, a frequent challenge for the pediatric urologist, leads to renal damage, if deobstruction is delayed. Several but sometimes unsatisfactory animal models have been developed to study this phenomenon. Obstruction created by surgical manipulation lacks adequate correlation with a developing congenital obstruction. In some animals with congenital hydronephrosis, evidence of renal obstruction is absent. A study of the renal morphology of rats with hereditary unilateral hydronephrosis has exhibited clear evidence of renal obstruction distinguishable from renal dilation. The renal mRNA expression of renin and transforming-growth factor-beta(1) (TGF-beta(1)) was measured by a semiquantitative RT-PCR technique. In hydronephrotic kidneys, a marked loss of parenchyma, atrophy and dilation of tubuli and collecting ducts and interstitial fibrosis was observed. The mRNA expression of renin was increased significantly in comparison to controls, whereas the contralateral kidneys showed renin activity below control levels. TGF-beta(1) expression was markedly increased in hydronephrotic kidneys, whereas contralateral kidneys did not differ significantly from control values. These data suggest the presence of renal obstruction and not only renal dilatation in these rats with congenital hydronephrosis. This colony seems to be a representative animal model to study congenital renal obstruction even in the fetal period without the need of surgical manipulation."],["dc.identifier.isi","000086978700006"],["dc.identifier.pmid","10850632"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/17980"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.issn","0300-5623"],["dc.title","Histologic and molecular evidence of obstructive uropathy in rats with hereditary congenital hydronephrosis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]
    Details PMID PMC WOS
  • 2004Journal Article
    [["dc.bibliographiccitation.firstpage","97"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","International Journal of Oncology"],["dc.bibliographiccitation.lastpage","105"],["dc.bibliographiccitation.volume","24"],["dc.contributor.author","Grzmil, M."],["dc.contributor.author","Voigt, S."],["dc.contributor.author","Thelen, Paul"],["dc.contributor.author","Hemmerlein, Bernhard"],["dc.contributor.author","Helmke, K."],["dc.contributor.author","Burfeind, Peter"],["dc.date.accessioned","2018-11-07T10:52:41Z"],["dc.date.available","2018-11-07T10:52:41Z"],["dc.date.issued","2004"],["dc.description.abstract","In order to analyze differential gene expression of putative prostate tumor markers we compared the expression levels of >400 cancer-related genes using the cDNA array technique in a set of prostate tumors and matched normal prostate tissues. Up-regulated expression of mammary tumor 8 kDa protein (MAT-8), complement component C1S (C1S), ferritin heavy chain (FTH1), peptidyl-prolyl cis-trans isomerase A (PPIA), RNA-binding protein regulatory subunit DJ-1 protein (DJ-1) and vacuolar ATP synthase subunit F (ATP6V1F) was determined in prostate carcinoma and confirmed by using quantitative real-time RT-PCR analyses. Furthermore, quantitative real time RT-PCR on intact RNAs from 11 paired laser microdissected epithelial tissue samples confirmed up-regulated MAT-8 expression in 6 out of 11 prostate tumors. To determine the function of MAT-8 in vitro, human PC-3 and LNCaP prostate carcinoma cells were transfected with small interfering double-stranded RNA (siRNA) oligonucleotides against the MAT-8 gene leading to a specific down-regulation of MAT-8 expression. In addition, suppression of MAT-8 expression caused a significant decrease in cellular proliferation of both prostate cancer cell lines, whereas invasive capacity and cellular apoptosis remained unaffected. Taken together, our results indicate that the human MAT-8 gene contains the potential to serve as a prostate cancer expression marker and that MAT-8 plays an important role in cellular growth of prostate carcinomas."],["dc.identifier.isi","000187359500012"],["dc.identifier.pmid","14654946"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/49171"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Professor D A Spandidos"],["dc.relation.issn","1019-6439"],["dc.title","Up-regulated expression of the MAT-8 gene in prostate cancer and its siRNA-mediated inhibition of expression induces a decrease in proliferation of human prostate carcinoma cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]
    Details PMID PMC WOS
  • 2008Journal Article
    [["dc.bibliographiccitation.firstpage","1606"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","Molecular Endocrinology"],["dc.bibliographiccitation.lastpage","1621"],["dc.bibliographiccitation.volume","22"],["dc.contributor.author","Kaulfuss, Silke"],["dc.contributor.author","Grzmil, Michal"],["dc.contributor.author","Hemmerlein, Bernhard"],["dc.contributor.author","Thelen, Paul"],["dc.contributor.author","Schweyer, Stefan"],["dc.contributor.author","Neesen, Juergen"],["dc.contributor.author","Bubendorf, Lukas"],["dc.contributor.author","Glass, Andrew G."],["dc.contributor.author","Jarry, Hubertus"],["dc.contributor.author","Auber, Bernd"],["dc.contributor.author","Burfeind, Peter"],["dc.date.accessioned","2018-11-07T11:13:42Z"],["dc.date.available","2018-11-07T11:13:42Z"],["dc.date.issued","2008"],["dc.description.abstract","In the present study, we demonstrate that leupaxin mRNA is overexpressed in prostate cancer (PCa) as compared with normal prostate tissue by using cDNA arrays and quantitative RT-PCR analyses. Moderate to strong expression of leupaxin protein was detected in approximately 22% of the PCa tissue sections analyzed, and leupaxin expression intensities were found to be significantly correlated with Gleason patterns/scores. In addition, different leupaxin expression levels were observed in PCa cell lines, and at the subcellular level, leupaxin was usually localized in focal adhesion sites. Furthermore, mutational analysis and transfection experiments of LNCaP cells using different green fluorescent protein-leupaxin constructs demonstrated that leupaxin contains functional nuclear export signals in its LD3 and LD4 motifs, thus shuttling between the cytoplasm and the nucleus. We could also demonstrate for the first time that leupaxin interacts with the androgen receptor in a ligand-dependent manner and serves as a transcriptional activator of this hormone receptor in PCa cells. Down-regulation of leupaxin expression using RNA interference in LNCaP cells resulted in a high rate of morphological changes, detachment, spontaneous apoptosis, and a reduction of prostate-specific antigen secretion. In contrast, knockdown of leupaxin expression in androgen-independent PC-3 and DU 145 cells induced a significant decrease of both the invasive capacity and motility. Our results therefore indicate that leupaxin could serve as a potential progression marker for a subset of PCa and may represent a novel coactivator of the androgen receptor. Leupaxin could function as a putative target for therapeutic interventions of a subset of advanced PCa."],["dc.identifier.doi","10.1210/me.2006-0546"],["dc.identifier.isi","000257144500008"],["dc.identifier.pmid","18451096"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6155"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/53958"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Endocrine Soc"],["dc.relation.issn","0888-8809"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Leupaxin, a novel coactivator of the androgen receptor, is expressed in prostate cancer and plays a role in adhesion and invasion of prostate carcinoma cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]
    Details DOI PMID PMC WOS
  • 2004Journal Article
    [["dc.bibliographiccitation.firstpage","25"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","International Journal of Oncology"],["dc.bibliographiccitation.lastpage","31"],["dc.bibliographiccitation.volume","24"],["dc.contributor.author","Thelen, Paul"],["dc.contributor.author","Schweyer, Stefan"],["dc.contributor.author","Hemmerlein, Bernhard"],["dc.contributor.author","Wuttke, Wolfgang"],["dc.contributor.author","Seseke, Florian"],["dc.contributor.author","Ringert, Rolf-Hermann"],["dc.date.accessioned","2018-11-07T10:52:41Z"],["dc.date.available","2018-11-07T10:52:41Z"],["dc.date.issued","2004"],["dc.description.abstract","Pathogenesis of prostate cancer is paralleled by aberrant transcriptional regulation which involves gene silencing by histone deacetylases. In cancer cells, inhibitors of histone deacetylases such as valproic acid can act as differentiation agents which relieve pro-apoptotic factors from transcriptional repression. We investigated the potential of the well-tolerated anticonvulsant valproic acid in prostate cancer cell line LNCaP and analyzed the activation of proapoptotic factors and resulting apoptosis. We used real time RT-PCR to quantify the mRNA expression of prostate-specific antigen, prostate-derived Ets transcription factor, tissue inhibitor of matrix metalloproteinase-3 and insulin-like growth factor binding protein-3. An automated sandwich-ELISA was used to measure secretion of prostate-specific antigen in conditioned cell culture media of LNCaP prostate cancer cells. Apoptotic cells were detected cytochemically and by applying immunocytochemistry. Activity of histone deacetylases in nuclear extracts was measured with a colorimetric assay kit. Valproic acid treatment caused a marked inhibition of histone deacetylases activity. Expression of prostate-derived Ets transcription factor and consequently prostate-specific antigen were down-regulated to basal levels in LNCaP cells. Pro-apoptotic factor caspase-3, tissue inhibitor of matrix metalloproteinase-3 and insulin-like growth factor binding protein-3 were up-regulated resulting in apoptosis of tumor cells. Valproic acid mediates marked effects on the expression of genes relevant in proliferation and apoptosis. Our study provides strong evidence that prostate cancer may benefit particularly from anti-proliferative stimuli from this well established drug."],["dc.identifier.isi","000187359500003"],["dc.identifier.pmid","14654937"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/49170"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Professor D A Spandidos"],["dc.relation.issn","1019-6439"],["dc.title","Expressional changes after histone deacetylase inhibition by valproic acid in LNCaP human prostate cancer cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]
    Details PMID PMC WOS