Thelen, Paul

[["dc.bibliographiccitation.firstpage","877"],["dc.bibliographiccitation.journal","INTERNATIONAL JOURNAL OF ONCOLOGY"],["dc.bibliographiccitation.lastpage","884"],["dc.bibliographiccitation.volume","32"],["dc.contributor.author","Possner, Maria"],["dc.contributor.author","Heuser, Markus"],["dc.contributor.author","Kaulfuss, Silke"],["dc.contributor.author","Scharf, Jens-Gerd"],["dc.contributor.author","Schulz, Wolfgang"],["dc.contributor.author","Ringert, Rolf-Hermann"],["dc.contributor.author","Thelen, Paul"],["dc.date.accessioned","2019-07-10T08:13:32Z"],["dc.date.available","2019-07-10T08:13:32Z"],["dc.date.issued","2008"],["dc.description.abstract","The function of the androgen-regulated homeobox protein NKX3.1 in prostate cancer is controversial. NKX3.1 is necessary for correct prostate development and undergoes frequent allelic loss in prostate cancer. However, no mutations occur in the coding region and some particularly aggressive cancers over-express the protein. Nevertheless NKX3.1 is often referred to as candidate tumor suppressor gene. Recent findings suggest a function in protection against oxidative damage involved in prostate carcinogenesis. Thus NKX3.1 may act differently at various stages of prostate cancer. Unlike a classical tumor suppressor NKX3.1 is up-regulated by androgens and down-regulated by phytoestrogens. In this study we performed RNAi based functional analysis by knocking down NKX3.1 expression in LNCaP prostate cancer cells and analyzing the impact of NKX3.1 on gene expression and cell proliferation. Knockdown of NKX3.1 evoked a massive down-regulation of NKX3.1 expression, followed by reduction in mRNA expression of the androdrogen receptor (AR) and the insulinlike growth factor receptor (IGF-1R). Western blot analysis showed strong decreases of NKX3.1, AR, and IGF-1R protein expression. Concomitantly, cell proliferation decreased and expression of prostate-specific antigen (PSA) mRNA and its secretion were diminished, whereas expression of IGF binding protein 3 (IGFBP-3) and MMP tissue inhibitor 3 (TIMP-3) was up-regulated. In tumor cells not deprived of NKX3.1 expression this gene still has a function which might differ from its role in prostate development and carcinogenesis. NKX3.1 knock-down altered the expression of genes highly relevant in prostate cancer cell proliferation and apoptosis. In LNCaP NKX3.1 most probably plays the role of an androgenregulated transcription factor whose down-regulation is paralleled by anti-proliferative and pro-apoptotic effects. Since NKX3.1 can regulate AR expression it may become a target for interference in hormone refractory prostate carcinoma."],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6151"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/61271"],["dc.language.iso","en"],["dc.notes.intern","Migrated from goescholar"],["dc.rights.access","closedAccess"],["dc.subject","NKX3.1; prostate cancer; tumor suppressor; RNA interference"],["dc.subject.ddc","610"],["dc.title","Functional analysis of NKX3.1 in LNCaP prostate cancer cells by RNA interference"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","16951"],["dc.bibliographiccitation.issue","24"],["dc.bibliographiccitation.journal","Oncotarget"],["dc.bibliographiccitation.lastpage","16961"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Bremmer, Felix"],["dc.contributor.author","Jarry, Hubertus"],["dc.contributor.author","Unterkircher, Valerie"],["dc.contributor.author","Kaulfuss, Silke"],["dc.contributor.author","Burfeind, Peter"],["dc.contributor.author","Radzun, Heinz-Joachim"],["dc.contributor.author","Ströbel, Philipp"],["dc.contributor.author","Thelen, Paul"],["dc.date.accessioned","2019-07-09T11:45:18Z"],["dc.date.available","2019-07-09T11:45:18Z"],["dc.date.issued","2018"],["dc.description.abstract","Novel treatments for castration-resistant prostate cancer (CRPC) such as abiraterone acetate (AA) or enzalutamide effectively target the androgen pathway to arrest aberrant signalling and cell proliferation. Testosterone is able to inhibit tumour cell growth in CRPC. Estrogen receptor-beta (ERβ) binds the testosteronemetabolites 3β-androstanediol and 3α-androstanediol in parallel to the canonical estradiol. In the prostate it is widely accepted that ERβ regulates estrogen signalling, mediating anti-proliferative effects. We used the prostate cancer cell lines LNCaP, PC-3, VCaP, and the non-neoplastic BPH-1. VCaP cells were treated with 1 nmol/L testosterone over 20 passages, yielding the cell line VCaPrev, sensitive to hormone therapies. In contrast, LNCaP cells were grown for more than 100 passages yielding a high passage therapy resistant cell line (hiPLNCaP). VCaP and hiPLNCaP cell lines were treated with 5 μmol/L AA for more than 20 passages, respectively, generating the AAtolerant- subtypes VCaPAA and hiPLNCaPAA. Cell lines were treated with testosterone, dihydrotestosterone (DHT), R1881, and the androgen-metabolites 3β-androstanediol and 3α-androstanediol. 3β-androstanediol or 3α-androstanediol significantly reduced proliferation in all cell lines except the BPH-1 and androgen receptor-negative PC-3 and markedly downregulated AR and estrogen receptor alpha (ERα). Whereas ERβ expression was increased in all cell lines except BPH-1 or PC-3. In summary, 3β-adiol or 3α-adiol, as well as DHT and R1881, significantly reduced tumour cell growth in CRPC cells. Thus, these compounds represent novel potential therapeutic approaches to overcome drug-resistance in CRPC, especially with regard to AR-V7 function in therapy resistance. Furthermore, these data confirm the tumour suppressor properties of ERβ in CRPC."],["dc.identifier.doi","10.18632/oncotarget.24763"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15104"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59207"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1949-2553"],["dc.rights","CC BY 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/3.0"],["dc.subject.ddc","610"],["dc.title","Testosterone metabolites inhibit proliferation of castration- and therapy-resistant prostate cancer"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]