Distribution of androgen receptor mRNA in the prepubertal male and female mouse brain

Journal of Neuroendocrinology

2021 Nov 14

Cara, A;Henson, E;Beekly, B;Elias, C;
| DOI: 10.1111/jne.13063

Androgens are steroid hormones that play a critical role in brain development and sexual maturation by acting upon both androgen receptors (AR), and estrogen receptors (ERα/β) after aromatization. The contribution of estrogens from aromatized androgens in brain development and the central regulation of metabolism, reproduction, and behavior is well defined, but the role of androgens acting on AR has been unappreciated. Here we map the sex specific expression of _Ar_ in the adult and developing mouse brain. Postnatal days (PND) 12 and 21 were used to target a critical window of prepubertal development. Consistent with previous literature in adults, sex-specific differences in _Ar_ expression were most profound in the bed nucleus of the stria terminalis (BST), medial amygdala (MEA), and medial preoptic area (MPO). _Ar_ expression was also high in these areas in PND 12 and 21 of both sexes. In addition, we describe extra-hypothalamic and extra-limbic areas which show moderate, consistent, and similar _Ar_ expression in both sexes at both prepubertal time points. Briefly, _Ar_ expression was observed in olfactory areas of the cerebral cortex, in the hippocampus, several thalamic nuclei, and cranial nerve nuclei involved in autonomic sensory and motor function. To further characterize forebrain populations of _Ar_ expressing neurons and determine whether they also coexpress estrogen receptors, we examined expression of _Ar_, _Esr1_, and _Esr2_ in prepubertal mice in selected nuclei. We found populations of neurons in the BST, MEA, and MPO that coexpress _Ar_, but not _Esr1_ or _Esr2_, while others express a combination of the three receptors. Our findings indicate that various brain areas express _Ar_ during prepubertal development and may play an important role in female neuronal development and physiology.

Defining potential targets of prenatal androgen excess: expression analysis of androgen receptor on hypothalamic neurons in the fetal female mouse brain

Journal of Neuroendocrinology

2023 May 18

Watanabe, Y;Fisher, L;Campbell, R;Jasoni, C;
| DOI: 10.1111/jne.13302

Polycystic ovary syndrome (PCOS) is a female endocrine disorder that is associated with prenatal exposure to excess androgens. In prenatally androgenized (PNA) mice that model PCOS, GABAergic neural transmission to and innervation of GnRH neurons is increased. Evidence suggests that elevated GABAergic innervation originates in the arcuate nucleus (ARC). We hypothesised that GABA-GnRH circuit abnormalities are a direct consequence of PNA, resulting from DHT binding to androgen receptor (AR) in the prenatal brain. However, whether prenatal ARC neurons express AR at the time of PNA treatment is presently unknown. We used RNAScope _in situ_ hybridization to localize AR mRNA (_Ar_)-expressing cells in healthy gestational day (GD) 17.5 female mouse brains and to assess co-expression levels in specific neuronal phenotypes. Our study revealed that less than 10% of ARC GABA cells expressed _Ar_. In contrast, we found that ARC kisspeptin neurons, critical regulators of GnRH neurons, were highly co-localised with _Ar_. Approximately 75% of ARC _Kiss1_-expressing cells also expressed _Ar_ at GD17.5, suggesting that ARC kisspeptin neurons are potential targets of PNA. Investigating other neuronal populations in the ARC we found that approximately 50% of pro-opiomelanocortin (_Pomc_) cells, 22% of tyrosine hydroxylase (_Th_) cells, 8% of agouti-related protein (_Agrp_) cells and 8% of somatostatin (_Sst_) cells express _Ar_. Lastly, RNAscope in coronal sections showed _Ar_ expression in the medial preoptic area (mPOA), and the ventral part of the lateral septum (vLS). These _Ar_-expressing regions were highly GABAergic, and 22% of GABA cells in the mPOA and 25% of GABA cells in the vLS also expressed _Ar_. Our findings identify specific neuronal phenotypes in the ARC, mPOA and vLS that are androgen sensitive in late gestation. PNA-induced functional changes in these neurons may be related to the development of impaired central mechanisms associated with PCOS-like features.

Analytic Validation of RNA In Situ Hybridization (RISH) for AR and AR-V7 Expression in Human Prostate Cancer.

Clin Cancer Res.

2016 May 10

Guedes L, Morais C, Almutairi F, Haffner MC, Zheng Q, Isaacs JT, Antonarakis ES, Lu C, Tsai H, Luo J, De Marzo AM, Lotan TL.
PMID: 27166397 | DOI: -

Abstract

PURPOSE:

RNA expression of androgen receptor splice variants may be a biomarker of resistance to novel androgen deprivation therapies in castrate resistant prostate cancer (CRPC). We analytically validated an RNA in situ hybridization (RISH) assay for total AR and AR-V7 for use in formalin fixed paraffin embedded (FFPE) prostate tumors.

EXPERIMENTAL DESIGN:

We used prostate cell lines and xenografts to validate chromogenic RISH to detect RNA containing AR exon 1 (AR-E1, surrogate for total AR RNA species) and cryptic exon 3 (AR-CE3, surrogate for AR-V7 expression). RISH signals were quantified in FFPE primary tumors and CRPC specimens, comparing to known AR and AR-V7 status by immunohistochemistry and RT-PCR.

RESULTS:

The quantified RISH results correlated significantly with total AR and AR-V7 levels by RT-PCR in cell lines, xenografts and autopsy metastases. Both AR-E1 and AR-CE3 RISH signals were localized in nuclear punctae in addition to the expected cytoplasmic speckles. Compared to admixed benign glands, AR-E1 expression was significantly higher in primary tumor cells with a median fold increase of 3.0 and 1.4 in two independent cohorts (p<0.0001 and p=0.04, respectively). While AR-CE3 expression was detectable in primary prostatic tumors, levels were substantially higher in a subset of CRPC metastases and cell lines, and were correlated with AR-E1 expression.

CONCLUSIONS:

RISH for AR-E1 and AR-CE3 is an analytically valid method to examine total AR and AR-V7 RNA levels in FFPE tissues. Future clinical validation studies are required to determine whether AR RISH is a prognostic or predictive biomarker in specific clinical contexts.

MYO10 promotes transzonal projection (TZP)-dependent germ line-somatic contact during mammalian folliculogenesis

Biology of reproduction

2022 Apr 26

Granados-Aparici, S;Volodarsky-Perel, A;Yang, Q;Anam, S;Tulandi, T;Buckett, W;Son, WY;Younes, G;Chung, JT;Jin, S;Terret, MÉ;Clarke, HJ;
PMID: 35470858 | DOI: 10.1093/biolre/ioac078

Granulosa cells of growing ovarian follicles elaborate filopodia-like structures termed transzonal projections (TZPs) that supply the enclosed oocyte with factors essential for its development. Little is known, however, of the mechanisms underlying the generation of TZPs. We show in mouse and human that filopodia, defined by an actin backbone, emerge from granulosa cells in early-stage primary follicles and that actin-rich TZPs become detectable as soon as a space corresponding to the zona pellucida appears. mRNA encoding Myosin10 (MYO10), a motor protein that accumulates at the base and tips of filopodia and has been implicated in their initiation and elongation, is present in granulosa cells and oocytes of growing follicles. MYO10 protein accumulates in foci located mainly between the oocyte and innermost layer of granulosa cells, where it co-localizes with actin. In both mouse and human, the number of MYO10 foci increases as oocytes grow, corresponding to the increase in the number of actin-TZPs. RNAi-mediated depletion of MYO10 in cultured mouse granulosa cell-oocyte complexes is associated with a 52% reduction in the number of MYO10 foci and a 28% reduction in the number of actin-TZPs. Moreover, incubation of cumulus-oocyte complexes in the presence of epidermal growth factor, which triggers a 93% reduction in the number of actin-TZPs, is associated with a 55% reduction in the number of MYO10 foci. These results suggest that granulosa cells possess an ability to elaborate filopodia, which when directed towards the oocyte become actin-TZPs, and that MYO10 increases the efficiency of formation or maintenance of actin-TZPs.

Deletion of androgen receptors from kisspeptin neurons prevents PCOS features in a letrozole mouse model

Endocrinology

2023 May 16

Decourt, C;Watanabe, Y;Evans, MC;Inglis, MA;Fisher, LC;Jasoni, CL;Campbell, RE;Anderson, GM;
PMID: 37191144 | DOI: 10.1210/endocr/bqad077

Polycystic ovarian syndrome (PCOS) is the leading cause of anovulatory infertility and is a heterogenous condition associated with a range of reproductive and metabolic impairments. While its etiology remains unclear, hyperandrogenism and impaired steroid negative feedback have been identified as key factors underpinning the development of PCOS-like features both clinically and in animal models. We tested the hypothesis that androgen signaling in kisspeptin-expressing neurons, which are key drivers of the neuroendocrine reproductive axis, is critically involved in PCOS pathogenesis. To this end, we used a previously validated letrozole (LET)-induced hyperandrogenic mouse model of PCOS in conjunction with Cre-lox technology to generate female mice exhibiting kisspeptin-specific deletion of androgen receptor (KARKO mice) to test whether LET-treated KARKO females are protected from the development of reproductive and metabolic PCOS-like features. LET-treated mice exhibited hyperandrogenism, and KARKO mice exhibited a significant reduction in the coexpression of kisspeptin and androgen receptor mRNA compared to controls. In support of our hypothesis, LET-treated KARKO mice exhibited improved estrous cyclicity, ovarian morphology, and insulin sensitivity in comparison to LET-treated control females. However, KARKO mice were not fully protected from the effects of LET-induced hyperandrogenism and still exhibited reduced corpora lutea numbers and increased body weight gain. These data indicate that increased androgen signaling in kisspeptin-expressing neurons plays a critical role in PCOS pathogenesis, but highlight that other mechanisms are also involved.

Deletion of Androgen Receptor in LepRb Cells Improves Estrous Cycles in Prenatally Androgenized Mice

Endocrinology

2023 Jan 23

Cara, AL;Burger, LL;Beekly, BG;Allen, SJ;Henson, EL;Auchus, RJ;Myers, MG;Moenter, SM;Elias, CF;
PMID: 36683455 | DOI: 10.1210/endocr/bqad015

Androgens are steroid hormones crucial for sexual differentiation of the brain and reproductive function. In excess, however, androgens may decrease fertility as observed in polycystic ovary syndrome, a common endocrine disorder characterized by oligo/anovulation and/or polycystic ovaries. Hyperandrogenism may also disrupt energy homeostasis, inducing higher central adiposity, insulin resistance, and glucose intolerance, which may exacerbate reproductive dysfunction. Androgens bind to androgen receptors (AR), which are expressed in many reproductive and metabolic tissues, including brain sites that regulate the hypothalamo-pituitary-gonadal axis and energy homeostasis. The neuronal populations impacted by androgen excess, however, have not been defined. We and others have shown that, in mice, AR is highly expressed in leptin receptor (LepRb) neurons, particularly in the arcuate (ARH) and the ventral premammillary nuclei (PMv). Here, we assessed if LepRb neurons, which are critical in the central regulation of energy homeostasis and exert permissive actions on puberty and fertility, have a role in the pathogenesis of female hyperandrogenism. Prenatally androgenized (PNA) mice lacking AR in LepRb cells (LepRbΔAR) show no changes in body mass, body composition, glucose homeostasis, or sexual maturation. They show, however, a remarkable improvement of estrous cycles combined with normalization of ovary morphology compared to PNA controls. Our findings indicate that the prenatal androgenization effects on adult reproductive physiology (i.e., anestrus and anovulation) are mediated by a subpopulation of LepRb neurons directly sensitive to androgens. They also suggest that the effects of hyperandrogenism on sexual maturation and reproductive function in adult females are controlled by distinct neural circuits.

Characterization of novel cell lines derived from a MYC-driven murine model of lethal metastatic adenocarcinoma of the prostate

Prostate.

2018 May 30

Markowski MC, Hubbard GK, Hicks JL, Zheng Q, King A, Esopi D, Rege A, Yegnasubramanian S, Bieberich CJ, De Marzo AM.
PMID: 29851094 | DOI: 10.1002/pros.23657

Abstract

BACKGROUND:

Loss or mutation of PTEN alleles at 10q23 in combination with 8q24 amplification (encompassing MYC) are common findings in aggressive, human prostate cancer. Our group recently developed a transgenic murine model of prostate cancer involving prostate-specific Pten deletion and forced expression of MYC under the control of the Hoxb13 promoter. MYC overexpression cooperated with Pten loss to recapitulate lethal, human prostate cancer.

METHOD:

We now report on the generation of two mouse prostate cancer cell lines, BMPC1 and BMPC2, derived from a lymph node, and liver metastasis, respectively.

RESULTS:

Both cell lines demonstrate a phenotype consistent with adenocarcinoma and grew under standard tissue culture conditions. Androgen receptor (AR) protein expression is minimal (BMPC1) or absent (BMPC2) consistent with AR loss observed in the BMPC mouse model of invasive adenocarcinoma. Growth in media containing charcoal-stripped serum resulted in an increase in AR mRNA in BMPC1 cells with no effect on protein expression, unless androgens were added, in which case AR protein was stabilized, and showed nuclear localization. AR expression in BMPC2 cells was not effected by growth media or treatment with androgens. Treatment with an anti-androgen/castration or androgen supplemented media did not affect in vitro or in vivo growth of either cell line, irrespective of nuclear AR detection.

DISCUSSION:

These cell lines are a novel model of androgen-insensitive prostatic adenocarcinoma driven by MYC over-expression and Pten loss.

Expression pattern of androgen receptor and AR-V7 in androgen deprivation therapy naïve salivary duct carcinomas

Hum Pathol.

2018 Sep 26

Yang RK, Zhao P, Lu C, Luo J, Hu R.
PMID: 30267779 | DOI: 10.1016/j.humpath.2018.09.009

Androgen deprivation therapy (ADT) has been used to treat salivary duct carcinoma (SDC). The androgen receptor splice variant-7 (AR-V7) has been detected in castration-resistant prostate cancer (CRPC) and implicated in resistance to androgen receptor (AR)-targeted therapies. Given the potential role of AR/AR-V7 in SDC treatment, this study focuses on AR/AR-V7 expression in SDC specimens collected prior to ADT. RNA in situ hybridization (ISH) and immunohistochemistry (IHC) to detect total AR and AR-V7 were performed on formalin-fixed, paraffin-embedded SDC specimens from 23 patients. Full length AR (AR-FL) and AR-V7 transcripts were quantified in a subset of tumors by reverse transcription polymerase chain reaction (RT-PCR). Twenty SDCs were positive for total AR by ISH and IHC. Among AR positive SDCs, 70% (14/20) were positive for AR-V7 mRNA by ISH, while 15% (3/20) were positive for AR-V7 protein by IHC. The three SDCs which expressed the highest levels of AR-V7 were all from female patients; one of them expressed significant amount of AR-V7 and barely detectable AR-FL transcripts by RT-PCR. Immunohistochemistry expression of Forkhead box protein A1, prostate-specific antigen, prostatic acid phosphatase, NKX3.1 was observed in some SDCs regardless of patient gender. Five SDCs demonstrated strong human epidermal growth factor receptor 2 (HER2) expression. We conclude that treatment-naïve SDCs may express AR-V7 at levels comparable to or even exceeding the levels detected in CRPC. Our data support the feasibility to incorporate AR-V7 assessment via ISH and/or IHC in the ongoing clinical trials evaluating the therapeutic benefit of AR targeted therapies in SDC patients.

Filopodia-Mediated Basement Membrane Assembly at Tumor Boundaries

SSRN Electronic Journal

2022 Mar 22

Peuhu, E;Jacquemet, G;Scheel, C;Isomursu, A;Paatero, I;Thol, K;Georgiadou, M;Guzman, C;Koskinen, S;Laiho, A;Elo, L;Boström, P;Hartiala, P;van Rheenen, J;Ivaska, J;
| DOI: 10.2139/ssrn.4059526

Ductal carcinoma in situ (DCIS) is a pre-invasive stage of breast cancer, where the tumor is encapsulated by a basement membrane (BM). At the invasive phase, the BM barrier is compromised enabling tumor cells to escape into the surrounding stroma. The molecular mechanisms that establish and maintain an epithelial BM barrier in vivo are poorly understood. Myosin-X (MYO10) is a filopodia-inducing motor protein implicated in metastasis and poor clinical outcome in patients with invasive breast cancer (IBC). We compared MYO10 expression in patient-matched normal breast tissue and DCIS lesions and found elevated MYO10 expression in DCIS samples, suggesting that MYO10 might facilitate the transition from DCIS to IBC in vivo. Indeed MYO10 promoted the formation of filopodia and cell invasion in vitro and positively regulated individual cancer cell dissemination from IBC lesions in vivo. However, MYO10-depleted DCIS xenografts were, unexpectedly, more invasive in vivo. In these xenografts, MYO10 depletion compromised BM formation around tumor acini resulting in poorly defined tumor borders and increased cancer cell dispersal into the surrounding stroma. Moreover, MYO10-depleted tumors showed increased EMT-marker-positive cells, specifically at the tumor periphery. We also observed cancer spheroids undergoing rotational motion and recruiting BM components in a filopodia-dependent manner to generate a near-continuous extracellular matrix boundary. Taken together, our data identify a protective role for MYO10 in early-stage breast cancer, where MYO10-dependent tumor cell protrusions support BM assembly at the tumor-stroma interface to limit cancer progression, and a pro-invasive role that facilitates cancer cell dissemination at later stages.

Analytical Validation and Clinical Qualification of a New Immunohistochemical Assay for Androgen Receptor Splice Variant-7 Protein Expression in Metastatic Castration-resistant Prostate Cancer

European Urology

2016 Apr 23

Jonathan Welti J, Rodrigues DN, Sharp A, Sun S, Lorentea D, Riisnaes R, Figueiredo I, Zafeiriou Z, Rescigno P, de Bono JS, Plymate SR.
PMID: - | DOI: 10.1016/j.eururo.2016.03.049

Abstract

Background
The androgen receptor splice variant-7 (AR-V7) has been implicated in the development of castration-resistant prostate cancer (CRPC) and resistance to abiraterone and enzalutamide.

Objective
To develop a validated assay for detection of AR-V7 protein in tumour tissue and determine its expression and clinical significance as patients progress from hormone-sensitive prostate cancer (HSPC) to CRPC.

Design, setting, and participants
Following monoclonal antibody generation and validation, we retrospectively identified patients who had HSPC and CRPC tissue available for AR-V7 immunohistochemical (IHC) analysis.

Outcome measurements and statistical analysis
Nuclear AR-V7 expression was determined using IHC H score (HS) data. The change in nuclear AR-V7 expression from HSPC to CRPC and the association between nuclear AR-V7 expression and overall survival (OS) was determined.

Results and limitations
Nuclear AR-V7 expression was significantly lower in HSPC (median HS 50, interquartile range [IQR] 17.5–90) compared to CRPC (HS 135, IQR 80–157.5; p < 0.0001), and in biopsy tissue taken before (HS 80, IQR 30–136.3) compared to after (HS 140, IQR 105–167.5; p = 0.007) abiraterone or enzalutamide treatment. Lower nuclear AR-V7 expression at CRPC biopsy was associated with longer OS (hazard ratio 1.012, 95% confidence interval 1.004–1.020; p = 0.003). While this monoclonal antibody primarily binds to AR-V7 in PC biopsy tissue, it may also bind to other proteins.

Conclusions
We provide the first evidence that nuclear AR-V7 expression increases with emerging CRPC and is prognostic for OS, unlike antibody staining for the AR N-terminal domain. These data indicate that AR-V7 is important in CRPC disease biology; agents targeting AR splice variants are needed to test this hypothesis and further improve patient outcome from CRPC.

Patient summary
In this study we found that levels of the protein AR-V7 were higher in patients with advanced prostate cancer. A higher level of AR-V7 identifies a group of patients who respond less well to certain prostate cancer treatments and live for a shorter period of time.

Rapid Loss of RNA Detection by In Situ Hybridization in Stored Tissue Blocks and Preservation by Cold Storage of Unstained Slides

American Journal of Clinical Pathology

2017 Oct 09

Baena-Del Valle JA, Zheng Q, Hicks JL, Trock HFBJ, Morrissey C, Corey E, Cornish TC, Sfanos KS, De Marzo AM.
PMID: - | DOI: 10.1093/ajcp/aqx094

Abstract

Objectives

Recent commercialization of methods for in situ hybridization using Z-pair probe/branched DNA amplification has led to increasing adoption of this technology for interrogating RNA expression in formalin-fixed, paraffin-embedded (FFPE) tissues. Current practice for FFPE block storage is to maintain them at room temperature, often for many years.

Methods

To examine the effects of block storage time on FFPE tissues using a number of RNA in situ probes with the Advanced Cellular Diagnostic’s RNAscope assay.

Results

We report marked reductions in signals after 5 years and significant reductions often after 1 year. Furthermore, storing unstained slides cut from recent cases (<1 year old) at –20°C can preserve hybridization signals significantly better than storing the blocks at room temperature and cutting the slides fresh when needed.

Conclusions

We submit that the standard practice of storing FFPE tissue blocks at room temperature should be reevaluated to better preserve RNA for in situ hybridization.

Regulation of AR mRNA translation in response to acute AR pathway inhibition

Nucleic acids research

2021 Dec 23

Somasekharan, SP;Saxena, N;Zhang, F;Beraldi, E;Huang, JN;Gentle, C;Fazli, L;Thi, M;Sorensen, PH;Gleave, M;
PMID: 34939643 | DOI: 10.1093/nar/gkab1247

We report a new mechanism of androgen receptor (AR) mRNA regulation and cytoprotection in response to AR pathway inhibition (ARPI) stress in prostate cancer (PCA). AR mRNA translation is coordinately regulated by RNA binding proteins, YTHDF3 and G3BP1. Under ambient conditions m6A-modified AR mRNA is bound by YTHDF3 and translationally stimulated, while m6A-unmodified AR mRNA is bound by G3BP1 and translationally repressed. When AR-regulated PCA cell lines are subjected to ARPI stress, m6A-modified AR mRNA is recruited from actively translating polysomes (PSs) to RNA-protein stress granules (SGs), leading to reduced AR mRNA translation. After ARPI stress, m6A-modified AR mRNA liquid-liquid phase separated with YTHDF3, while m6A-unmodified AR mRNA phase separated with G3BP1. Accordingly, these AR mRNA messages form two distinct YTHDF3-enriched or G3BP1-enriched clusters in SGs. ARPI-induced SG formation is cell-protective, which when blocked by YTHDF3 or G3BP1 silencing increases PCA cell death in response to ARPI stress. Interestingly, AR mRNA silencing also delays ARPI stress-induced SG formation, highlighting its supportive role in triggering this stress response. Our results define a new mechanism for stress adaptive cell survival after ARPI stress involving SG-regulated translation of AR mRNA, mediated by m6A RNA modification and their respective regulatory proteins.

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	Description
sense Example: Hs-LAG3-sense	Standard probes for RNA detection are in antisense. Sense probe is reverse complent to the corresponding antisense probe.
Intron# Example: Mm-Htt-intron2	Probe targets the indicated intron in the target gene, commonly used for pre-mRNA detection
Pool/Pan Example: Hs-CD3-pool (Hs-CD3D, Hs-CD3E, Hs-CD3G)	A mixture of multiple probe sets targeting multiple genes or transcripts
No-XSp Example: Hs-PDGFB-No-XMm	Does not cross detect with the species (Sp)
XSp Example: Rn-Pde9a-XMm	designed to cross detect with the species (Sp)
O# Example: Mm-Islr-O1	Alternative design targeting different regions of the same transcript or isoforms
CDS Example: Hs-SLC31A-CDS	Probe targets the protein-coding sequence only
EnEm	Probe targets exons n and m
En-Em	Probe targets region from exon n to exon m
Retired Nomenclature
tvn Example: Hs-LEPR-tv1	Designed to target transcript variant n
ORF Example: Hs-ACVRL1-ORF	Probe targets open reading frame
UTR Example: Hs-HTT-UTR-C3	Probe targets the untranslated region (non-protein-coding region) only
5UTR Example: Hs-GNRHR-5UTR	Probe targets the 5' untranslated region only
3UTR Example: Rn-Npy1r-3UTR	Probe targets the 3' untranslated region only
Pan Example: Pool	A mixture of multiple probe sets targeting multiple genes or transcripts

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Probes for INS

Content for comparison

Gene

Product

Research area

Category

Abstract

PURPOSE:

EXPERIMENTAL DESIGN:

RESULTS:

CONCLUSIONS:

Abstract

Background
The androgen receptor splice variant-7 (AR-V7) has been implicated in the development of castration-resistant prostate cancer (CRPC) and resistance to abiraterone and enzalutamide.

Objective
To develop a validated assay for detection of AR-V7 protein in tumour tissue and determine its expression and clinical significance as patients progress from hormone-sensitive prostate cancer (HSPC) to CRPC.

Design, setting, and participants
Following monoclonal antibody generation and validation, we retrospectively identified patients who had HSPC and CRPC tissue available for AR-V7 immunohistochemical (IHC) analysis.

Outcome measurements and statistical analysis
Nuclear AR-V7 expression was determined using IHC H score (HS) data. The change in nuclear AR-V7 expression from HSPC to CRPC and the association between nuclear AR-V7 expression and overall survival (OS) was determined.

Patient summary
In this study we found that levels of the protein AR-V7 were higher in patients with advanced prostate cancer. A higher level of AR-V7 identifies a group of patients who respond less well to certain prostate cancer treatments and live for a shorter period of time.

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Advanced Cell Diagnostics

Bio-Techne

Advanced Cell Diagnostics China

Probes for INS

Content for comparison

Gene

Product

Research area

Category

Abstract

PURPOSE:

EXPERIMENTAL DESIGN:

RESULTS:

CONCLUSIONS:

Abstract

BackgroundThe androgen receptor splice variant-7 (AR-V7) has been implicated in the development of castration-resistant prostate cancer (CRPC) and resistance to abiraterone and enzalutamide.

ObjectiveTo develop a validated assay for detection of AR-V7 protein in tumour tissue and determine its expression and clinical significance as patients progress from hormone-sensitive prostate cancer (HSPC) to CRPC.

Design, setting, and participantsFollowing monoclonal antibody generation and validation, we retrospectively identified patients who had HSPC and CRPC tissue available for AR-V7 immunohistochemical (IHC) analysis.

Outcome measurements and statistical analysisNuclear AR-V7 expression was determined using IHC H score (HS) data. The change in nuclear AR-V7 expression from HSPC to CRPC and the association between nuclear AR-V7 expression and overall survival (OS) was determined.

Patient summaryIn this study we found that levels of the protein AR-V7 were higher in patients with advanced prostate cancer. A higher level of AR-V7 identifies a group of patients who respond less well to certain prostate cancer treatments and live for a shorter period of time.

Pages

Advanced Cell Diagnostics

Bio-Techne

Advanced Cell Diagnostics China

Background
The androgen receptor splice variant-7 (AR-V7) has been implicated in the development of castration-resistant prostate cancer (CRPC) and resistance to abiraterone and enzalutamide.

Objective
To develop a validated assay for detection of AR-V7 protein in tumour tissue and determine its expression and clinical significance as patients progress from hormone-sensitive prostate cancer (HSPC) to CRPC.

Design, setting, and participants
Following monoclonal antibody generation and validation, we retrospectively identified patients who had HSPC and CRPC tissue available for AR-V7 immunohistochemical (IHC) analysis.

Outcome measurements and statistical analysis
Nuclear AR-V7 expression was determined using IHC H score (HS) data. The change in nuclear AR-V7 expression from HSPC to CRPC and the association between nuclear AR-V7 expression and overall survival (OS) was determined.

Patient summary
In this study we found that levels of the protein AR-V7 were higher in patients with advanced prostate cancer. A higher level of AR-V7 identifies a group of patients who respond less well to certain prostate cancer treatments and live for a shorter period of time.