Non-enrichment-based method for analysis of androgen receptor expression in circulating tumor cells (CTCs) in patients with metastatic castrate-resistant prostate cancer.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 194-194 ◽  
Author(s):  
Mitchell E. Gross ◽  
Daniel Lazar ◽  
Edward H Cho ◽  
Madelyn Luttgen ◽  
Thomas Metzner ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Positive Association ◽  
Total Cell ◽  
Receptor Expression ◽  
Normal Blood ◽  
Cell Area ◽  
Nuclear Area ◽  
Lncap Cells ◽  
High Definition

194 Background: We have established a fluid phase biopsy approach that identifies CTCs which preserves cytologic features in high-definition (HD) for diagnostic pathology without using immune or surface receptor-based enrichment. HD-CTCs identified with this approach can be used for enumeration and molecular characterization. Methods: Blood was collected from metastatic prostate cancer patients and normal donors in Cyto-Chex tubes (Streck, Omaha, NE) as part of IRB approved protocols at each site. Following erythrocyte lysis, 3 million nucleated cells were deposited on a glass slide. Samples were incubated with a pan-cytokeratin (CK), CD45, and androgen receptor (AR) antibodies and counter-stained with DAPI. LNCaP cells were spiked into normal blood. Images were obtained with a fluorescent scanning microscope and analyzed with a computer algorithm. Candidate HD-CTCs were subsequently verified by expert readers. Slides were re-imaged for quantitative analysis using at a fixed exposure and gain. Results: A total of 227 CTCs from ten patients were compared to 20 LNCaP cells. The median (range) HD-CTCs in this cohort was: 9 (1-62) cells/ml. The mean ± standard deviation measurements in HD-CTCs were observed: CK intensity 60.4±154; total cell area 89.0 ± 53.8 µm2; nuclear area 61.1 ± 36.0 µm2. LNCaP cells spiked into normal blood gave the following values: CK intensity 1166+/−306; total cell area 143 ± 48.1 µm2; nuclear area 63.1 ± 18.6 µm2. CTCs were additionally classified as either AR positive (AR+) or AR negative (AR−). 37 of the 227 (16.3%) HD-CTCs were AR+. The average CK intensity was significantly higher in AR+ versus AR− cells at 174.23 and 39.86, respectively (p<0.001). The AR expression intensity in AR+ HD-CTCs and LNCaP cells was comparable at 979.4 and 902.2, respectively (p=0.824). Conclusions: We find a positive association between AR and CK expression on a per cell basis. Further, we find AR is expressed at comparable levels in CTCs from patients and human prostate cancer cells in culture. The HD-CTC based approach may be used for enumeration and molecular interrogation of CTCs in patients with prostate cancer.

scholarly journals Role of Testosterone Levels on the Combinatorial Effect of Boswellia serrata Extract and Enzalutamide on Androgen Dependent LNCaP Cells and in Patient Derived Cells

2021 ◽  
Vol 20 ◽  
pp. 153473542199682
Author(s):  
Prathesha Pillai ◽  
Ginil Kumar Pooleri ◽  
Shantikumar V. Nair
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Early Stage ◽  
Therapeutic Option ◽  
Specific Antigen ◽  
Cell Killing ◽  
Receptor Expression ◽  
Lncap Cells ◽  
Boswellia Serrata ◽  
Physiological Serum

Co-therapy with herbal extracts along with current clinical drugs is being increasingly recognized as a useful complementary treatment for cancer. The anti-cancer property of the phyto-derivative acetyl-11 keto β boswellic acid (AKBA) has been studied in many cancers, including prostate cancer. However, the whole extract of the gum resin Boswellia serrata (BS) and anti-androgen enzalutamide has not been explored in prostate cancer to date. We hypothesized that the BS extract containing 30% (AKBA) with enzalutamide acted synergistically in the early phase of cancer, especially in LNCaP cells, by inhibiting androgen receptor (AR) and by reducing cell proliferation, and further, that the extract would be superior to the action of the active ingredient AKBA when used alone or in combination with enzalutamide. To test our hypothesis, we treated LNCaP cells with BS extract or AKBA and enzalutamide both individually and in combination to analyze cell viability under different levels of dihydrotestosterone (DHT). The inhibition of androgen receptor (AR) followed by the expression of prostate-specific antigen (PSA) and the efflux mechanism of the cells were analyzed to determine the effect of the combination on the cellular mechanism. Cells derived from prostate cancer patients were also tested with the combination. Only 6 µM enzalutamide along with BS in the range of 4.1 µg/ml to 16.4 µg/ml gave the best synergistic results with nearly 50% cell killing even though standard enzalutamide doses were as high as 48 µM. Cell killing was most effective at intermediate DHT concentrations of approximately 1 nM, which corresponds to normal physiological serum levels of DHT. The Pgp expression level and the androgen receptor expression levels were reduced under the combination treatment; the former helping to minimize drug efflux and the latter by reducing the sensitivity to hormonal changes. Furthermore, the combination reduced the PSA level secreted by the cells. In contrast, AKBA could not achieve the needed synergism for adequate cell killing at equivalent concentrations. The combination of enzalutamide and BS extract containing 30% AKBA because of their synergistic interaction is an attractive therapeutic option for treating early stage (hormone-dependent) prostate cancer and is superior to the use of AKBA alone.

scholarly journals Interplay of Nuclear Factor-κB and B-myb in the Negative Regulation of Androgen Receptor Expression by Tumor Necrosis Factor α

2008 ◽  
Vol 22 (2) ◽  
pp. 273-286 ◽  
Author(s):  
Soyoung Ko ◽  
Liheng Shi ◽  
Soyoung Kim ◽  
Chung S. Song ◽  
Bandana Chatterjee
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Thyroid Hormone Receptor ◽  
Nuclear Factor Κb ◽  
Negative Regulation ◽  
Receptor Expression ◽  
Nuclear Factor ◽  
Lncap Cells ◽  
Down Regulation ◽  
Androgen Independent

Abstract Increased androgen receptor (AR) levels are associated with prostate cancer progression to androgen independence and therapy resistance. Evidence has suggested that chronic inflammation is closely linked to various cancers including prostate cancer. Herein we show that the proinflammatory cytokine TNFα negatively regulates AR mRNA and protein expression and reduces androgen sensitivity in androgen-dependent LNCaP human prostate cancer cells. Decreased AR expression results from transcription repression involving essential in cis interaction of nuclear factor-κB (NF-κB) with the B-myb transcription factor at a composite genomic element in the 5′-untranslated region of AR. The negative regulation was abrogated when NF-κB activity was inhibited by a superrepressor of the inhibitory κB protein. In contrast, androgen-independent C4-2 (LNCaP-derived) cells fail to show AR down-regulation by TNFα, despite expression of B-myb and TNFα-induced NF-κB activity similar to that in LNCaP cells. The negatively regulated AR gene chromatin region showed TNFα-dependent enrichment of B-myb and the NF-κB proteins p65 and p50. In parallel, the histone deacetylase 1, corepressor silencing mediator of retinoid and thyroid hormone receptor and the corepressor-associated scaffold protein mSin3A were recruited to the inhibitory site. In C4-2 cells, neither NF-κB and B-myb, nor any of the corepressor components, were detected at the negative site in response to TNFα. Apoptosis was induced in TNFα-treated LNCaP cells, likely in part due to the down-regulation of AR. The androgen-independent, AR-expressing C4-2 and C4-2B (derived from C4-2) cells were resistant to TNFα-induced apoptosis. The results linking androgen dependence to the NF-κB and AR pathways may be insightful in identifying novel treatment targets for prostate cancer.

Anti-androgen receptor activity of apoptotic CK2 inhibitor CX4945 in human prostate cancer LNCap cells

2012 ◽  
Vol 22 (17) ◽  
pp. 5470-5474 ◽  
Author(s):  
Byung Jun Ryu ◽  
Seung-hwa Baek ◽  
Jiyeon Kim ◽  
Su Jung Bae ◽  
Sung-Youn Chang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Receptor Activity ◽  
Human Prostate ◽  
Human Prostate Cancer ◽  
Lncap Cells ◽  
Androgen Receptor Activity ◽  
Ck2 Inhibitor

scholarly journals Androgen Receptor Expression of Prostate Cancer Correlates with Gleason Score and Perineural Invasion in West Sumatera, Indonesia

2020 ◽  
Vol 7 (11) ◽  
pp. 5125-5129
Author(s):  
Anandia Putriyuni ◽  
Meta Zulyati Oktora
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Gleason Score ◽  
Cancer Progression ◽  
Perineural Invasion ◽  
Receptor Expression ◽  
Grade Group ◽  
Who Grade ◽  
Who Grade Group ◽  
Histopathological Grading

Prostate cancer is the second most common and the fifth leading cause of death by cancer in men worldwide now. The failure of androgen deprivation therapy (ADT) for prostate cancer caused by activated androgen receptor (AR) signaling pathways mostly found. The role of AR in growth and progression of prostate cancer is still unclear. Analysis of AR expression in prostate cancer has never been done in West Sumatera. This study aims to determine AR expression of prostate cancer and correlate with Gleason score and perineural invasion. A total of 56 prostate cancer from department of anatomical pathology in West Sumatera. Hematoxylin and eosin (HE) stained slides and paraffin blocks were retrieved. Slides of all cases were evaluated to review Gleason score, histopathological grading, WHO grade group based on ISUP 2014/WHO 2016 and perineural invasion. Androgen receptor immunohistochemistry (IHC) was applied on all cases. High AR expression was the mostly found (51,79%). The mostly prostate cancer is Gleason score 9 (44,64%), histopathological grading poorly differentiated/undifferentiated (76,78%), WHO grade group 5 (48,21%). Perineural invasion was noted in 39,29%. There was significant statistical correlation between AR expression and Gleason score, but no significant correlation with perineural invasion. AR expression is the important marker of prostate cancer progression.

scholarly journals Inhibiting Multiple Deubiquitinases to Reduce Androgen Receptor Expression in Prostate Cancer Cells

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Alicia de las Pozas ◽  
Teresita Reiner ◽  
Virginia De Cesare ◽  
Matthias Trost ◽  
Carlos Perez-Stable
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Cancer Cells ◽  
Receptor Expression ◽  
Androgen Receptor Expression ◽  
Prostate Cancer Cells

scholarly journals Emerging Therapeutic Activity of Davallia formosana on Prostate Cancer Cells through Coordinated Blockade of Lipogenesis and Androgen Receptor Expression

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 914
Author(s):  
Po-Fan Hsieh ◽  
Wen-Ping Jiang ◽  
Shih-Yin Huang ◽  
Praveenkumar Basavaraj ◽  
Jin-Bin Wu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Fatty Acid ◽  
Androgen Receptor ◽  
Molecular Basis ◽  
Fatty Acid Synthase ◽  
Specific Antigen ◽  
Receptor Expression ◽  
Migration And Invasion ◽  
Therapeutic Activity ◽  
Castration Resistant

Background: Prostate cancer (PCa) is the most prevalent malignancy diagnosed in men in Western countries. There is currently no effective therapy for advanced PCa aggressiveness, including castration-resistant progression. The aim of this study is to evaluate the potential efficacy and determine the molecular basis of Davallia formosana (DF) in PCa. Methods: LNCaP (androgen-sensitive) and C4-2 (androgen-insensitive/castration-resistant) PCa cells were utilized in this study. An MTT-based method, a wound healing assay, and the transwell method were performed to evaluate cell proliferation, migration, and invasion. Intracellular fatty acid levels and lipid droplet accumulation were analyzed to determine lipogenesis. Moreover, apoptotic assays and in vivo experiments were conducted. Results: DF ethanol extract (DFE) suppressed proliferation, migration, and invasion in PCa cells. DFE attenuated lipogenesis through inhibition of the expression of sterol regulatory element-binding protein-1 (SREBP-1) and fatty acid synthase (FASN). Moreover, DFE decreased androgen receptor (AR) and prostate-specific antigen (PSA) expression in PCa cells. We further showed the potent therapeutic activity of DFE by repressing the growth and leading to apoptosis of subcutaneous C4-2 tumors in a xenograft mouse model. Conclusions: These data provide a new molecular basis of DFE in PCa cells, and co-targeting SREBP-1/FASN/lipogenesis and the AR axis by DFE could be employed as a novel and promising strategy for the treatment of PCa.

Pharmacological inhibition of androgen receptor expression induces cell death in prostate cancer cells

2020 ◽  
Vol 77 (22) ◽  
pp. 4663-4673 ◽  
Author(s):  
In-Sung Song ◽  
Yu Jeong Jeong ◽  
Jueun Kim ◽  
Kyoung-Hwa Seo ◽  
Nam-In Baek ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Death ◽  
Androgen Receptor ◽  
Cancer Cells ◽  
Receptor Expression ◽  
Androgen Receptor Expression ◽  
Prostate Cancer Cells ◽  
Pharmacological Inhibition
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