Searchable abstracts of presentations at key conferences in endocrinology
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Androgens 2016

ea0042p1 | (1) | Androgens2016

Inhibition of NADPH oxidase 4 attenuates stromal activation associated with prostate cancer

Sampsona Natalie , Szyndralewiez Cedric , Klocker Helmut

Carcinoma-associated fibroblasts (CAFs) within the stromal tumor microenvironment play a key role in promoting the development, progression and therapy resistance of prostate cancer (PCa). However, the stromal compartment is not targeted by current treatment strategies. Elevated secretion of transforming growth factor beta (TGFβ) by epithelial cells in prostate intraepithelial neoplasia (PIN) lesions and tumor cells induces fibroblast activation to the CAF phenotype and i...

ea0042p2 | (1) | Androgens2016

Functional analysis of the AR LBD dimerization surface

Helsen Christine , Prekovic Stefan , van Royen Martin E , Houtsmuller Adriaan B , Fuentes-Prior Pablo , Estebanez-Perpina Eva , Claessens Frank

The androgen receptor (AR) is a multidomain transcription factor consisting of an aminoterminal domain (NTD), a DNA binding domain (DBD) and a ligand binding domain (LBD). Binding of androgens marks the start of a sequence of intra- and interdomain communications, DNA binding, coregulator recruitment and gene activation. Besides the DBD-mediated dimerization on the DNA, there is a functionally relevant N/C interaction. The contribution of the intra- and intermolecular N/C inte...

ea0042p3 | (1) | Androgens2016

Diminished response of prostate cancer cells to antiandrogens upon co-culture with cancer-associated fibroblasts as shown in a 3-dimensional prostate cancer epithelial-stromal organoid model

Eder Theresa , Weber Anja , Neuwirt Hannes , Grunbacher Georg , Schafer Georg , Ploner Christian , Klocker Helmut , Sampson Natalie , Eder Iris E

The use of more tissue-mimetic 3-dimensional (3D) cell culture models for in vitro drug screening has significantly increased in the past with the expectation to overcome with over-interpretation of drug effects obtained with conventional 2D cultures. In this study, we characterized 3D prostate cancer (PCa) organoids where PCa epithelial cells (LNCaP, DuCaP, LAPC4) were cultured alone or with PCa-associated fibroblasts (CAFs) in 96 well hanging drop plates in order to...

ea0042p4 | (1) | Androgens2016

Expression of a novel androgen-regulated long noncoding RNA correlates with progression-free survival in prostate cancer patients

Kohvakka Annika , Kivinummi Kati , Kytola Ville , Ylipaa Antti , Annala Matti , Urbanucci Alfonso , Nykter Matti , Visakorpi Tapio

Prostate cancer (PC) is the second most frequently diagnosed cancer in men worldwide. 10–20% of the PC patients develop castration-resistant prostate cancer (CRPC) that has no curative therapies. There are also no effective prognostic markers to predict emergence of CRPCs. Long noncoding RNAs (lncRNAs) are a recently found group of RNAs that are not translated into proteins. Many of them are found to be differentially expressed in cancer, and shown to have a regulative ro...

ea0042p5 | (1) | Androgens2016

Androgen pathway regulating microRNAs in prostate cancer progression and therapy

Kalofonou Foteini , Fletcher Claire , Waxman Jonathan , Bevan Charlotte

Prostate cancer is an androgen dependent malignancy that initially responds well to androgen ablation therapy. However treatment, castrate resistant prostate cancer eventually emerges. Even in that phase of the disease, the androgen receptor (AR) still seems to play a role. MicroRNAs are small (19–25nt) non-coding RNAs that modulate gene silencing through inhibition of translation and mRNA degradation. They are considered to be master regulators of gene expression and act...

ea0042p6 | (1) | Androgens2016

The bi-directional interaction of AR and IL6 signalling in the response to enzalutamide in prostate cancer cells

Handle Florian , Erb Holger HH , Luef Birgit , Hoefer Julia , Dietrich Dimo , Parson Walther , Kristiansen Glen , Santer Frederic R , Culig Zoran

Chronic inflammation and high expression of pro-inflammatory cytokines, such as Interleukin-6 (IL6), are well-known risk factors for prostate cancer (PCa). IL6 is known to activate the androgen receptor (AR) and has been implicated in development of castration resistance. Therefore, we wanted to investigate the interaction of AR and IL6 signalling and the effect on anti-androgen treatment. We could confirm IL6 mediated activation of the AR on 3 AR target genes in presence of R...

ea0042p7 | (1) | Androgens2016

μ-Crystalline as hormone antagonist in prostate cancer

Merkel Olaf , Aksoy Osman , Suzani Martin , Hassler Melanie , Schlangen Karin , Balber Theresa , Mitterhauser Markus , Moazzami Ali , Schlederer Michaela , Turner Suzanne , Egger Gerda , Hormann Gregor , Hacker Markus , Culig Zoran , Pencik Jan , Kenner Lukas

Prostate cancer (PCa) is the most frequent cancer in men in the western world. PCa growth is highly dependent on androgens and androgen ablation is the cornerstone of current therapeutic approaches. μ-Crystalline (CRYM) is the main component of the kangaroohs eye’s lens. CRYM binds thyroid hormone (T3) in a NADPH dependent manner thereby sequestering it from being transcriptionally active in the nucleus. The role of CRYM in prostate cancer is largely unknown. This st...

ea0042p8 | (1) | Androgens2016

Antiandrogens reduce intratumoral androgen concentrations and induce androgen receptor expression in castration-resistant VCaP xenografts

Knuuttila Matias , Mehmood Arfa , Huhtaniemi Riikka , Oksala Riikka , Hakkinen Merja , Laajala Teemu D , Aittokallio Tero , Auriola Seppo , Ohlsson Claes , Elo-Uhlgren Laura , Sipila Petra , Makela Sari , Poutanen Matti

The growth of prostate cancer (PCa) can be suppressed by androgen deprivation therapy (ADT). However, in a significant proportion of men receiving ADT PCa progresses to castration-resistant prostate cancer, associated with activation of intratumoral androgen biosynthesis and induced androgen receptor (AR) expression. Accordingly, we have recently shown that the castration-resistant VCaP (CR-VCaP) xenografts express high level of AR and retain detectable intratumoral androgen c...

ea0042p9 | (1) | Androgens2016

The deubiquitinating enzyme USP12 controls prostate cancer cell survival by regulating the AR-AKT-p53 signalling network

McClurg Urszula L , Chit Nay C T H , Nakjang Sirintra , Edwards Joanne , McCracken Stuart R , Robson Craig N

We previously demonstrated that USP12 functions as an AR co-activator by directly deubiquitinating the AR and stabilising its protein levels. Additionally, we showed that USP12 targets the PHLPP AKT phosphatases leading to decreased levels of activated, phosphorylated AKT (pAKT) and as such indirectly stabilises the AR preventing its phosphorylation at serine 213. We further investigated the role of USP12 in prostate cancer by analysing the transcriptome of the LNCaP prostate ...

ea0042p10 | (1) | Androgens2016

Metastases-prone localized prostate cancer: a genomic analysis

Van den Broeck Thomas , Gevaert Thomas , Prekovic Stefan , Boeckx Bram , Smeets Elien , Ong Kaye , Lehrer Jonathan , Haddad Zaid , Erho Nicholas , Helsen Christine , Lambrechts Diether , Buerki Christine , Davicioni Elai , Joniau Steven , Claessens Frank

Clinical features of the primary prostate tumor remain insufficient for clinicians to accurately define patients at highest risk of developing metastases. However, the primary tumor is the source of these metastases, and thus should contain information on its metastatic potential. We hypothesized that the combination of a primary tumor’s copy number alterations (CNAs) and genome-wide transcriptome information would give us more insight in the biology of metastases-prone l...

ea0042p11 | (1) | Androgens2016

Switch to succinate-mediated mitochondrial respiration associated with HIF-1α stabilization in PTEN negative prostate cancer cells

Weber Anja , Pencik Jan , Kenner Lukas , Klocker Helmut , Eder Iris E

Metabolic reprogramming resulting in significant alterations of the energy metabolism is a hallmark of prostate cancer (PCa). In this study we performed a comprehensive metabolic analysis of various human (LNCaP, DuCaP, PC-3, Du145) and murine PCa cell lines differing in the expression of the tumor suppressor phosphatase and tensin homolog (PTEN). In line with previous studies we found that PTEN- PCa cells (LNCaP, PC-3) had a higher glycolytic activity than PTEN<sup...

ea0042p12 | (1) | Androgens2016

Exploiting pioneer factors of androgen receptor variants for novel prostate cancer therapies

Chaytor Lewis , Gaughan Luke

Prostate cancer (PC) growth is androgen-dependent, hence, the mainstay for treatment is hormone-ablation therapy using anti-androgens, and/or androgen-deprivation therapies. Unfortunately, after a median time of 18 months, the cancer reappears in an androgen independent form, termed castrate-resistant PC (CRPC), which is largely fatal. To date, many molecular mechanisms have been suggested to be responsible for persistent AR signalling in CRPC. AR variants (AR-Vs), short forms...

ea0042p13 | (1) | Androgens2016

Lysine demethylase 7A (KDM7A) as a potential therapeutic target in prostate cancer

Metzler Veronika M , de Brot Simone , Whitchurch Jonathan , Robinson Brian D , Boorjian Stephen , Gudas Lorraine J , Johannson Martin , Persson Jenny L , Heery David M , Mongan Nigel P

Androgen Receptor (AR) is central to prostate cancer (PCa) tumorigenesis and metastases. The genomic actions of androgens are mediated by the AR in complex with multiple chromatin modifying coregulators. We and others have identified lysine demethylases (KDMs) as important mediators of androgen signaling and increased expression of specific coregulators, including KDM1A, are implicated in PCa recurrence. There is an urgent need for new PCa treatments. While androgen deprivatio...

ea0042p14 | (1) | Androgens2016

Androgen receptor variants and microenvironment in prostate cancer

Schreyer Edwige , Erdmann Eva , Cottard Felicie , Delbecque Marine , Berthelemy Pauline , Kurtz Jean-Emmanuel , Ceraline Jocelyn

Androgen ablation therapy remains the most common treatment for patients with advanced prostate cancer (PCa). However, most patients relapse and develop a castration-resistant PCa. The emergence of androgen receptor (AR) variants, such as constitutively active ARs, has been involved in this failure to androgen deprivation. Nevertheless, the tumour microenvironment is another necessary feature driving PCa progression. Cancer associated fibroblasts (CAFs) are one of the speciali...

ea0042p15 | (1) | Androgens2016

Altered steroid profiles in prostate cancer xenograft model with low ADRB2 levels

Ramberg Hakon , Kellman Ralf , Braadland Peder Rustoen , Staerli Elin , Waagene Stein , Mellgren Gunnar , Maelandsmo Gunhild Mari , Tasken Kristin Austlid

It has been established in recent years that androgens are involved in the progression of castration resistant prostate cancer (CRPC). Although androgen deprivation therapy reduces the level of androgens and inhibits the androgen receptor, there are studies reporting that the androgen signaling axis is still involved in the development of CRPC. We have in a previous study shown that low level of β2-adrenergic receptor (ADRB2) is associated with shorter time to ...

ea0042p16 | (1) | Androgens2016

Identification of protein kinases involved in AR transcriptional regulation in prostate cancer

Walker Scott , Banks Peter , Robson Craig , Coffey Kelly

Phosphorylation of the Androgen Receptor (AR), has been shown to play an important role in directly modulating AR activity. However, the full extent of which protein kinases are involved in the regulation of the AR remains unknown. In order to address which kinases are important in the regulation of AR activity in both androgen sensitive and independent prostate cancer (PCa), a comprehensive siRNA kinome screen was performed. AR transcriptional regulation was evaluated using a...

ea0042p17 | (1) | Androgens2016

Next generation sequencing panels to predict response to hormonal therapy in prostate cancer

Kallio Heini M L , Annala Matti , Brofeldt Anniina , Hieta Reija , Kivinummi Kati , Tammela Teuvo , Nykter Matti , Lilja Hans G , Bova G Steven , Visakorpi Tapio

Prostate cancer (PC) is the most common malignancy and third most common cause of cancer-related death among men in Europe. Although most PCs grow slowly, 20–25% of the patients believed to have organ-confined disease will experience biochemical recurrence already during 5-years of follow-up. The standard treatment against advanced PC is androgen deprivation (ADT). Unfortunately, androgen deprivation treatment eventually fails leading to the emergence of castration resist...

ea0042p18 | (1) | Androgens2016

Altering androgen precursor availability impacts on endometrial function

Gibson Douglas A , Kelepouri Olympia , Simitsidellis Ioannis , Critchley Hilary O D , Saunders Philippa T K

The establishment of pregnancy requires dynamic remodelling of the endometrium. Decidualization, a key part of this process, is characterised by differentiation of endometrial stromal fibroblasts (ESF) which secrete factors that regulate implantation and placental development. We recently discovered that ESF synthesise androgens which modulate the expression of endometrial receptivity and decidualization markers. Utilisation of the circulating androgen precursor DHEA within ta...

ea0042p19 | (1) | Androgens2016

The AR/NCOA1 signaling regulates prostate cancer migration by involvement of PRKD1

Luef Birgit , Handle Florian , Kharaishvili Gvantsa , Hager Martina , Rainer Johannes , Janetschek Gunter , Hruby Stephan , Englberger Christine , Bouchal Jan , Santer Frederic R , Culig Zoran

Due to the urgent need for new prostate cancer (PCa) therapies, the role of androgen receptor (AR) interacting proteins should be investigated. In this study we aimed to address whether the AR coactivator nuclear receptor coactivator 1 (NCOA1) is involved in PCa progression. Therefore, we tested the effect of long-term NCOA1 knockdown on processes relevant to metastasis formation. [3H]-thymidine incorporation assays revealed a reduced proliferation rate in ...

ea0042p20 | (1) | Androgens2016

Combined AR phosphorylation at serine 81 and serine 213 are associated with decreased survival in Castrate Resistant Prostate Cancer

McAllister Milly J , McCall Pamela , Underwood Mark A , Leung Hing Y , Edwards Joanne

Current therapies for locally advanced or metastatic prostate cancer aim to inhibit androgen receptor (AR) activation directly or by depleting androgens via androgen deprivation therapy. However this therapeutic approach eventually fails in ~80% of patients, leading to development of castrate resistant prostate cancer (CRPC). There are currently few therapeutic options available for CRPC with limited prognostic or predictive biomarkers. The aim of the current study was to dete...

ea0042p21 | (1) | Androgens2016

Investigating the role of SUMOylation of androgen receptor splice variants by SUMO1 in castration resistant prostate cancer

Kounatidou Evangelia E , Gaughan Luke

Prostate cancer (PC) is currently the most commonly diagnosed non-cutaneous cancer affecting UK men. Androgen deprivation therapy (ADT) has traditionally been used as the gold standard treatment for advanced PC. Despite the initial response to androgen ablation, tumours relapse and become refractory to clinically approved anti-androgens, resulting in castration-resistant PC (CRPC). In CRPC, androgen receptor (AR) signalling is inappropriately restored by AR splice variants (AR...

ea0042p22 | (1) | Androgens2016

The cellular and molecular effects of the androgen receptor agonist, Cl-4AS-1, on breast cancer cells

Ahram Mamoun , Mustafa Ebtihal , Hammad Shatha Abu , Hodhod Mariam , Zihlif Malek

The notable expression of the androgen receptor (AR) in breast cancer suggests an important biological role and, hence, a window of utilizing it as a therapeutic target. Due to the undesirable side effects of AR agonists, attempts have been undertaken to develop tissue-selective androgen receptor modulators (SARMs). One such SARM is Cl-4AS-1, which has previously been shown to behave similar to the natural AR agonist, dihydrotestosterone (DHT). We aimed to examine the effects ...

ea0042p23 | (1) | Androgens2016

Characterising mechanisms of aberrant androgen receptor signalling in advanced prostate cancer

Guo Wenrui , Robson Craig , Gaughan Luke

Although new treatments for castrate-resistant prostate cancer (CRPC), such as enzalutamide and abiraterone, have shown promise, moderate response rates and development of resistance to these agents has limited their clinical effectiveness. It is therefore vital we improve our understanding of androgen receptor (AR) re-activation in advanced disease, focusing particularly on regulatory processes governing activity of AR mutants and splice variants (AR-Vs), to enable the develo...

ea0042p24 | (1) | Androgens2016

Identification and characterization of a CRM1/XPO1-dependent nuclear export signal in the human androgen receptor

Schutz Stefanie V , Merseburger Axel , Azoitei Anca , Cronauer Marcus V

There is experimental evidence that inhibition of the glycogen synthase kinase-3β (GSK-3β) by small molecule inhibitors induces a rapid, CRM1/XPO1-dependent nuclear export of the AR protein in human prostate cancer cell lines. By contrast nucleo-cytoplasmic shuttling of Q641X, a C-terminally truncated AR-mutant, remains unaffected by GSK-3β inhibition. In silico analysis of the AR C-terminus (amino acids [aa] 641-920) predicted two putative NES-sites, l...

ea0042p25 | (1) | Androgens2016

Mitochondrial function and mitochondrial heteroplasmy levels differ between benign and malignant prostate tissue.

Schopf Bernd , Schafer Georg , Weissensteiner Hansi , Gnaiger Erich , Klocker Helmut

Mitochondria play a vital role in cellular bioenergetics, providing energy via oxidative phosphorylation (OXPHOS) and metabolic intermediates. Aerobic ATP production is orchestrated by a multi-enzyme complex, which uses the electrons gained during oxidation of energy substrates to generate an electrochemical potential across the mitochondrial (mt) membrane that drives ATP synthase. Although there is evidence that mitochondrial function as well as mtDNA mutations might play a r...

ea0042p26 | (1) | Androgens2016

Mechanisms behind tumor relapse in 22Rv1 xenografts after treatment with abiraterone or cabazitaxel

Ylitalo Erik Bovinder , Wikstrom Pernilla

Castration-resistant prostate cancer (CRPC) develops after androgen deprivation therapy of advanced PC, often with metastatic growth in bone and very poor prognosis. Standard treatment is docetaxel, followed by androgen-synthesis (abiraterone) or androgen receptor inhibition, or treatment with the novel taxane cabazitaxel. Novel drugs are constantly under development and molecular properties of individual tumors will determine treatment effectiveness in individual cases. The a...

ea0042p27 | (1) | Androgens2016

The amino terminal domain of steroid hormone receptors as a novel drug target: Identification of small molecule inhibitors

Monaghan Amy E. , McElroy Stuart , McEwan Iain J.

The role of the androgen receptor (AR) in the progression of prostate cancer (PCa) is well established. Competitive inhibition of the AR ligand binding domain (LBD) has been the staple of antiandrogen therapies employed to combat the disease in recent years. However their efficacy has often been limited by the emergence of resistance, mediated through point mutations and receptor truncations. As a result the prognosis for patients with malignant castrate resistant disease rema...

ea0042p28 | (1) | Androgens2016

Evidence for neuroendocrine progenitor cells in a transgene mouse model of prostate cancer

Udovica Simon , Otahal Alexander , Tomasich Erwin , Heller Gerwin , Schwarz Michael , Spittler Andreas , Horvat Reinhard , Horak Peter , Marhold Maximilian , Krainer Michael

In developed countries, prostate cancer (PCa) is the most prevalent cancer and the second most common cause of cancer related death in males. Tumors from patients exhibiting disease progression after systemic androgen deprivation treatment (ADT), referred to as castration resistant prostate cancer (CRPC), often show differentiation towards an aggressive phenotype – neuroendocrine prostate cancer or NE-PC. In our study, we used the Simian-Virus 40 (SV-40) T-antigen driven ...

ea0042p29 | (1) | Androgens2016

Potential of Metabolome Analysis for new Insights into System Biology and Relevance for Translational Medicine

Koal Therese

All characteristic metabolic properties of a bio-fluid, cell, tissue or an organism are described by its metabolome, which is the functional readout of the genome and proteome. Metabolomics is the newest member in the “omics” cascade investigating the metabolome within a specific biological matrix (e.g. serum, tissue, cells or CSF) offering the possibility of assessing the relationship of a genetic modification to a specific desired phenotype in an effort to determin...

ea0042p30 | (1) | Androgens2016

Critical Role of Androgen Receptor Level in Prostate Cancer Cell Resistance to New Generation Antiandrogen Enzalutamide

Hoefer Julia , Akbor Mohammady , Handle Florian , Ofer Philipp , Puhr Martin , Parson Walther , Culig Zoran , Klocker Helmut , Heidegger Isabel

Enzalutamide is an androgen receptor (AR) inhibitor approved for therapy of metastatic castration resistant prostate cancer. However, clinical application revealed that 30 to 40% of patients acquire resistance after a short period of treatment. Currently, the molecular mechanisms underlying such insensitivities are not completely understood, partly due to a lack of model systems. In the present study we established three different cellular models of enzalutamide resistance inc...

ea0042p31 | (1) | Androgens2016

Mediators of stress resistance in prostate cancer cells

Pickard Adam , Amoroso Francesca , May-Stewart Lorna , McComb Jonathan , Mills Ian G.

The emergence of prostate cancer and the progression of the disease are significantly driven by the androgen receptor (AR) in combination with other transcription factors. The evolution of aggressive disease requires tumours to become resistant to metabolic stress and subsequently therapeutic stress. Given the role of the prostate gland has a secretory organ characterised by high rates of protein synthesis particularly in AR-positive luminal epithelial cells there are inherent...

ea0042p32 | (1) | Androgens2016

Differential expression and androgen regulation of microRNA molecules in breast cancer cells

Ahram Mamoun , Zaza Rand , Mustafa Ebtihal , Jarrar Heba , Al-Saber Razan , Hammad Shatha Abu , Zihlif Malek

MicroRNA molecules (miRNAs) have important roles in regulating cell behavior. In addition, their expression levels can be used in tumor classification. The expression of miRNAs has been to be regulated by the androgen receptor (AR), which seems to play an interesting role in the tumorigenic process of breast cancer. We hypothesized that AR may control the behavior of breast cancer cells via modulating the expression of miRNAs. Using PCR arrays, we examined the differential exp...

ea0042p33 | (1) | Androgens2016

Phosphorylation of androgen receptor at serine 81 by cyclin-dependent kinases

Skraškova Zuzana , Jorda Radek , Řezničkova Eva , Kryštof Vladimir

The androgen receptor (AR) is a steroid-hormone receptor that plays a crucial role in the normal development of male reproductive tissues. Its high expression and/or relaxation of its regulation are strongly implicated in prostate cancer (PCa). Androgen binding induces conformational changes of AR that influence its subcellular localization, interactions with other proteins, DNA binding and transcriptional activity. Androgen dependent is also AR(S81) phosphorylation. Phosphory...

ea0042p34 | (1) | Androgens2016

Mechanisms of radioresistance in prostate cells

Guggenberger Fabian , Erb Holger , Skvortsova Ira-Ida , Culig Zoran , Santer Frederic R.

Among androgen deprivation therapy (ADT), radiation therapy is an approved treatment either for early stage local PCa, but also for metastatic M1 stage PCa. However, tumour relapse is a frequent event that affects about 80% of patients undergoing prior treatment. There is increasing evidence that the occurrence of cancer stem cells (CSC) may play an important role in therapy resistance, in particular also in radioresistance. However, our knowledge on the mechanisms of radiores...

ea0042p35 | (1) | Androgens2016

Isolation, propagation and characterisation of primary prostate cancer epithelial cell lines from prostate specimens

Patek Samantha , McCall Pamela , Underwood Mark A , Edwards Joanne

Prostate cancer is the most common male cancer in the UK. Currently there is a lack of pre-clinical models to predict patient’s response to treatment for prostate cancer. Identifying which patients will respond best to treatment avoids exposing patients to treatment side effects unnecessarily. Primary cell culture provides a translational model to predict individual patient’s response to drug treatments. In this study, we develop a technique for isolation, propagatio...

ea0042p36 | (1) | Androgens2016

Androgen and Estrogen Receptor Co-regulation of Human UDP-glucuronosyltransferases 2B15 and 2B17 in Breast Cancer

Hu Dong Gui , Selth Luke , Tarulli Gerard , Meech Robyn , Wijayakumara Dhilushi , Chanawong Apichaya , Russell Roslin , Caldas Carlos , Robinson Jessica LL , Carroll Jason , Tilley Wayne , Mackenzie Peter , Hickey Theresa

Glucuronidation is an enzymatic process that terminally inactivates steroid hormones, including estrogens and androgens, thereby influencing carcinogenesis in hormone-dependent cancers. While estrogens drive breast carcinogenesis via the estrogen receptor alpha (ERα), androgens play a critical role as prohormones for estrogen biosynthesis and ligands for the androgen receptor (AR). Herein, the expression and regulation of two androgen inactivating UDP-glucuronosyltransfer...

ea0042p37 | (1) | Androgens2016

Abstract withdrawn....

ea0042p38 | (1) | Androgens2016

Histological modeling of prostate cancer

Ruusuvuori Pekka , Valkonen Mira , Kartasalo Kimmo , Visakorpi Tapio , Latonen Leena , Nykter Matti

Prostate cancer is multifocal in nature, and histological grading is the key clinical prognostic factor. To build non-subjective histological analysis tools, and to model the multifocality of prostate cancer within the organ, we use analysis of histological images to quantitatively describe prostate cancer. Our current effort shows how heterogeneity in prostate tissue due to cancer or spatial location can be quantified with image-derived features. We use high-resolution digita...

ea0042p39 | (1) | Androgens2016

Androgen receptor variant 7 induces cellular senescence

Kaya Zeynep , Lack Nathan A.

Androgen receptor (AR) signaling is critical at all stages of prostate cancer including chemically castrated late-stage forms of the disease. How the AR can initiate transcription in the absence of androgens has been proposed to occur through several mechanisms including the production of constitutively active androgen receptor variants. Lacking a ligand binding domain, these variants are intrinsically resistant to all clinically approved AR antagonists and have been found to ...

ea0042p40 | (1) | Androgens2016

Segment-specific enrichment of AP-2 and Runx motifs within caput- and IS-preferred androgen receptor binding sites in the mouse epididymis

Pihlajamaa Paivi , Sahu Biseajyoti , Janne Olli A. , Poutanen Matti , Sipila Petra

Epididymis is an androgen dependent organ with four main segments; initial segment (IS), caput, corpus and cauda. It is an essential site for post-testicular sperm maturation, as spermatozoa acquire fertilizing capacity during epididymal transit. Post-testicular maturation is dependent on the proteins expressed and secreted to the lumen by epididymal cells. Androgens regulate gene expression in epididymis in a segment-specific manner. Caput-specific genes are androgen regulate...

ea0042p41 | (1) | Androgens2016

Characterisation of Androgen and Estrogen Receptor Cross-Talk

Alkheilewi Mohammad , Bryan Rosie , Brooke Greg

Worldwide, breast cancer is the most common cancer to develop in women. Steroid receptors play a key role in the progression of the majority of breast cancer subtypes. Estrogen Receptor-α (ERα), for example drives the growth of approximately 70% of tumours and is therefore a useful therapeutic target for this disease. However, the Androgen Receptor (AR) is the highest expressed receptor in normal breast and appears to also play an important role in breast cancer. In ...

ea0042p42 | (1) | Androgens2016

High levels of the AR-V7 splice variant and co-amplification of the Golgi protein coding YIPF6 in AR amplified prostate cancer bone metastases

Djusberg Erik , Jernberg Emma , Thysell Elin , Golovleva Irina , Lundberg Pia , Crnalic Sead , Widmark Anders , Bergh Anders , Brattsand Maria , Wikstrom Pernilla

The relation between androgen receptor (AR) gene amplification and other mechanisms behind castration-resistance in prostate cancer, such as increased expression of constitutively active AR variants and steroid-converting enzymes have been poorly examined. Specific aims of this study were to examine AR amplification in treatment-naïve and castration-resistant prostate cancer (CRPC) bone metastases and to explore molecular and functional differences. AR gene amplification ...