Current translational and basic prostate\ud
cancer research is limited by the number of\ud
cell lines that truly reflect the spectrum of\ud
disease progression, with most commonly\ud
used cell lines being derived from metastatic\ud
lesions. There are essentially no prostate\ud
cancer cell lines derived from primary\ud
tumours or localised disease in wide use

Batra, Jyotsna

Clements, Judith

Jovanovic, Lidija

Lawrence, Mitchell

McLennan, Elizabeth

Nelson, Colleen

Odorico, Dimitri M.

Rae, Fiona K.

Walpole, Carina

Williams, Elizabeth D.

Current translational and basic prostate cancer research is limited by the number of cell lines that truly reflect the spectrum of disease progression, with most commonly used cell lines being derived from metastatic lesions. There are essentially no prostate cancer cell lines derived from primary tumours or localised disease in wide use

Queensland University of Technology ePrints Archive

rnaseqbrowser or http://sourceforge.net/projects/rnaseqbrowser/075Impeding the adaptive response ofprostate cancer to androgentargeted therapies with relaxinreceptor antagonistGregor Tevz1, Akhter M Hossain2, NathalieBock1, Varinder Jeet1, Ross A Bathgate3,Elizabeth D Williams1, Melanie Lehman1,Dietmar W Hutmacher1, John D Wade2 andColleen C Nelson1,41Australian Prostate Cancer Research Centre– Queensland, Institute of Health andBiomedical Innovation, Queensland Universityof Technology, Princess Alexandra Hospital,Translational Research Institute, Brisbane,Australia2Florey Institute of Neuroscience and MentalHealth, School of Chemistry, University ofMelbourne, Parkville, Australia3Department of Neuroscience and MentalHealth, Florey Institute of Neuroscience andMental Health, University of Melbourne,Parkville, Australia4Vancouver Prostate Centre, DeObjective: Androgen deprivation andandrogen targeted therapies (ATT) areestablished treatments for prostate cancer(PCa). Although initially effective, ATTinduces an adaptive response that leads totreatment resistance. Increased expressionof relaxin-2 (RLN2) is an important alter-ation in the adaptive response. RLN2 has awell described role in PCa cell proliferation,adhesion and tumour growth. The objec-tives of this study were to develop cell mod-els for studies of RLN2 signalling and toimplement in vitro assays for evaluating thetherapeutic properties of the unique RLN2receptor (RXFP1) antagonist.Methods: To validate the increasedexpression of RLN2 after the ATT wetreated LNCaP cells with antiandrogensand used qPCR to determine its expres-sion. We established doxycycline inducibleRLN2 and RXFP1 knock-down (KD) andover-expression (OE) LNCaP models. Wechemically synthesised RXFP1 antagonistand evaluated its therapeutic properties incell proliferation and adhesion assays. Toidentify paracrine action of relaxin, we co-cultured inducible RLN2 KD and OELNCaP models on bioengineered osteo-blast matrices.Results: We confirmed the increasedexpression of RLN2 after ATT in LNCaPcells. We established and validated induc-ible RLN2 and RXFP1 KD and OE LNCaPmodels. We showed that the KD of RLN2and RXFP1 inhibited proliferation andadhesion of LNCaP cells. Our uniqueRXFP1 antagonist inhibited proliferationof LNCaP cells.Conclusions: Our results show that theinhibition of relaxin signalling supressedproliferation and adhesion of PCa cells.Further confirmation of these findings in apreclinical model will be crucial step fortranslation of the RXFP1 antagonist intoclinics.076Characterisation of novel primarytumour derived epithelial prostatecancer cell linesCarina Walpole1, Fiona Rae1, LidijaJovanovic1, Dimitri Odorico2, ElizabethMcLennan1, Mitchell Lawrence2, Colleen CNelson1, Elizabeth D Williams1,3, Jyotsna Batra1and Judith Clements11Australian Prostate Cancer Research Centre– Queensland, Institute of Health andBiomedical Innovation, Queensland Universityof Technology, Princess Alexandra Hospital,Translational Research Institute, Brisbane,Australia2Institute of Health and BiomedicalInnovation, Queensland University ofTechnology, Brisbane, Australia3Department of Surgery (St Vincent’sHospital), University of Melbourne, Melbourne,AustraliaCurrent translational and basic prostatecancer research is limited by the number ofcell lines that truly reflect the spectrum ofdisease progression, with most commonlyused cell lines being derived from meta-static lesions. There are essentially no pros-tate cancer cell lines derived from primarytumours or localised disease in wide use.Objective: The objective of this work is tocharacterise novel primary tumour derivedepithelial prostate cancer cell lines.Methods: We have established a numberof new prostate cancer cell lines derivedfrom radical prostatectomy tissue takenfrom men with localised disease. Pathologyof the tissue revealed benign and adeno-carcinoma phenotypes with Gleason scoresof 6–7 and patient PSA levels of 4–9 ng/mL. Cells were characterised for lineagemarkers, other prostate cancer relevanttargets, STR profiling, RNAseq analysisand functional assays.Results: RT-PCR and Western Blot analy-sis of lineage markers confirmed thesecells are luminal in origin (cytokeratin/CK8 and 18 positive), with low to no ARexpression. Most were also CK5, CK14and p63 positive, which are basal markers,and CD133 negative suggesting a mixedlineage but not stem cell like. In initialanchorage independent growth assays, nogrowth/colony formation was observed,however, cells appeared to remain viable.This phenomenon may be attributed totheir early tumour origins. Further charac-terisation of these lines is ongoing.Conclusions: These results show potentialfor these cell lines as model for primary/localised disease. Development of contem-porary cell lines, particularly from men withlocalised prostate cancer, will provide a rep-ertoire of more clinically relevant researchtools for the prostate cancer community.077A multiple nucleotide lengthpolymorphism (MNLP) mediatesandrogen regulation of IRX4 inprostate cancerJanaththani Panchadsaram, Gregor Tevz,Nataly Stylianou, Brett Hollier, Colleen CNelson, Judith Clements and Jyotsna BatraAustralian Prostate Cancer Research Centre –Queensland, Institute of Health andBiomedical Innovation, Queensland Universityof Technology, Princess Alexandra Hospital,Translational Research Institute, Brisbane,AustraliaObjective: Androgens and the androgenreceptor (AR) play a crucial role in theinitiation and progression of prostate can-cer (PCa), regulating the expression ofmany PCa risk-associated genes. IroquoisHomeobox 4 (IRX4) has been recentlyidentified with PCa risk and overexpressedin PCa. We observed a down-regulation ofIRX4 expression in the cells undergoingepithelial to mesenchymal transition, sug-gesting its potential role in PCa progres-sion and aim to delineate the androgen-mediated regulation of IRX4 in PCa.Methods: In-silico analysis to identify thetranscription factor (TF) binding sites reg-ulating the IRX4 expression (CistromeFinder database), followed by sequencingof these regions was performed. PCa celllines (DuCaP and LNCaP) were treatedwith androgens for 48 h and IRX4 expres-sion was determined by qRT-PCR.Results: Binding of two crucial TFs – ARand ERG, was observed upstream of IRX4in the VCaP cells while there was no ARbinding in LNCaP cells at this locus, sug-gesting differential androgen responsive-ness of IRX4. Moreover, IRX4 wasup-regulated by androgens in DuCaP cells,36 © 2015 The AuthorsBJU International © 2015 BJU International | 116, Supplement 1, 30--4936 Translational Science

Characterisation of novel primary tumour derived epithelial prostate cancer cell lines

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Characterisation of novel primary tumour derived epithelial prostate cancer cell lines

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