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Selective androgen receptor mediators

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https://www.readbyqxmd.com/read/28343791/androgen-receptor-deficient-islet-%C3%AE-cells-exhibit-alteration-in-genetic-markers-of-insulin-secretion-and-inflammation-a-transcriptome-analysis-in-the-male-mouse
#1
Weiwei Xu, Tianhua Niu, Beibei Xu, Guadalupe Navarro, Matthew J Schipma, Franck Mauvais-Jarvis
AIMS: Testosterone action is mediated via the androgen receptor (AR). We have reported that male mice lacking AR selectively in β-cells (βARKO(-/y)) develop decreased glucose-stimulated insulin secretion (GSIS), producing glucose intolerance. We showed that testosterone action on AR in β-cells amplifies the insulinotropic action of GLP-1 on its receptor via a cAMP-dependent protein kinase-A pathway. METHODS: To investigate AR-dependent gene networks in β-cells, we performed a high throughput whole transcriptome sequencing (RNA-Seq) in islets from male βARKO(-/y) and control mice...
March 9, 2017: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/28252832/inactivation-of-id4-promotes-a-crpc-phenotype-with-constitutive-ar-activation-through-fkbp52
#2
Jugal Bharat Joshi, Divya Patel, Derrick J Morton, Pankaj Sharma, Jin Zou, Dhanushka Hewa Bostanthirige, Yamini Gorantla, Peri Nagappan, Shravan Kumar Komaragiri, Jeffrey C Sivils, Huan Xie, Ravi Palaniappan, Guangdi Wang, Marc B Cox, Jaideep Chaudhary
Castration-resistant prostate cancer (CRPC) is the emergence of prostate cancer cells that have adapted to the androgen-depleted environment of the prostate. In recent years, targeting multiple chaperones and co-chaperones (e.g., Hsp27, FKBP52) that promote androgen receptor (AR) signaling and/or novel AR regulatory mechanisms have emerged as promising alternative treatments for CRPC. We have shown that inactivation of inhibitor of differentiation 4 (ID4), a dominant-negative helix loop helix protein, promotes de novo steroidogenesis and CRPC with a gene expression signature that resembles constitutive AR activity in castrated mice...
November 27, 2016: Molecular Oncology
https://www.readbyqxmd.com/read/28235766/sigma1-targeting-to-suppress-aberrant-androgen-receptor-signaling-in-prostate-cancer
#3
Jeffrey D Thomas, Charles G Longen, Halley M Oyer, Nan Chen, Christina M Maher, Joseph M Salvino, Blase Kania, Kelsey N Anderson, William F Ostrander, Karen E Knudsen, Felix J Kim
Suppression of androgen receptor (AR) activity in prostate cancer by androgen depletion or direct AR antagonist treatment, although initially effective, leads to incurable castration resistant prostate cancer (CRPC) via compensatory mechanisms including resurgence of AR and AR splice variant (ARV) signaling. Emerging evidence suggests that Sigma1 (also known as sigma-1 receptor) is a unique chaperone or scaffolding protein that contributes to cellular protein homeostasis. We reported previously that some Sigma1-selective small molecules can be used to pharmacologically modulate protein homeostasis pathways...
February 24, 2017: Cancer Research
https://www.readbyqxmd.com/read/28216900/trichosanthes-kirilowii-exerts-androgenic-activity-via-regulation-of-psa-and-klk2-in-22rv1-prostate-cancer-cells
#4
Soo-Jin Jeong, Ji-Yoon Choi, Mi-Sook Dong, Chang-Seob Seo, Hyeun-Kyoo Shin
BACKGROUND: The androgen comprises a group of hormones that play roles in male reproductive activity as well as personal characteristics. OBJECTIVE: We investigated the androgenic activity of various herbal medicines in human prostate cancer 22Rv1 cells. MATERIALS AND METHODS: Herbal extracts of Trichosanthes kirilowii (TK), Asarum sieboldii (AS), Sanguisorba officinalis (SO), and Xanthium strumarium (XS) were selected to have androgenic effects based on a preliminary in vitro screening system...
January 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/28130434/selective-progesterone-receptor-modulator-sprm-ulipristal-acetate-upa-and-its-effects-on-the-human-endometrium
#5
L H R Whitaker, A A Murray, R Matthews, G Shaw, A R W Williams, P T K Saunders, H O D Critchley
STUDY QUESTION: What is the impact of administration of the selective progesterone receptor modulator (SPRM), ulipristal acetate (UPA) on the endometrium of women with fibroids? SUMMARY ANSWER: UPA administration altered expression of sex-steroid receptors and progesterone-regulated genes and was associated with low levels of glandular and stromal cell proliferation. WHAT IS KNOWN ALREADY: Administration of all SPRM class members results in PAEC (progesterone receptor modulator associated endometrial changes)...
January 26, 2017: Human Reproduction
https://www.readbyqxmd.com/read/28112153/dissecting-cell-type-specific-roles-of-androgen-receptor-in-prostate-homeostasis-and-regeneration-through-lineage-tracing
#6
Qing Xie, Yueli Liu, Tao Cai, Corrigan Horton, Joshua Stefanson, Zhu A Wang
Androgen signals through androgen receptor (AR) to influence prostate development and cancer. How stromal and epithelial AR regulate prostate homeostasis remains unclear. Using genetic lineage tracing, we systematically investigated the role of cell-autonomous AR in different prostate epithelial cell types. Here we show that AR is dispensable for basal cell maintenance, but is cell-autonomously required for the luminal differentiation of rare basal stem cells. In contrast, AR deletion in luminal cells alters cell morphology and induces transient over-proliferation, without affecting androgen-mediated luminal cell survival or regeneration...
January 23, 2017: Nature Communications
https://www.readbyqxmd.com/read/28086790/rna-sequencing-for-global-gene-expression-associated-with-muscle-growth-in-a-single-male-modern-broiler-line-compared-to-a-foundational-barred-plymouth-rock-chicken-line
#7
Byung-Whi Kong, Nicholas Hudson, Dongwon Seo, Seok Lee, Bhuwan Khatri, Kentu Lassiter, Devin Cook, Alissa Piekarski, Sami Dridi, Nicholas Anthony, Walter Bottje
BACKGROUND: Modern broiler chickens exhibit very rapid growth and high feed efficiency compared to unselected chicken breeds. The improved production efficiency in modern broiler chickens was achieved by the intensive genetic selection for meat production. This study was designed to investigate the genetic alterations accumulated in modern broiler breeder lines during selective breeding conducted over several decades. METHODS: To identify genes important in determining muscle growth and feed efficiency in broilers, RNA sequencing (RNAseq) was conducted with breast muscle in modern pedigree male (PeM) broilers (n = 6 per group), and with an unselected foundation broiler line (Barred Plymouth Rock; BPR)...
January 13, 2017: BMC Genomics
https://www.readbyqxmd.com/read/27998958/bisphenol-a-and-its-analogues-disrupt-centrosome-cycle-and-microtubule-dynamics-in-prostate-cancer
#8
Shuk-Mei Ho, Rahul Rao, Sarah To, Emma Schoch, Pheruza Tarapore
Humans are increasingly exposed to structural analogues of bisphenol A (BPA), as BPA is being replaced by these compounds in BPA-free consumer products. We have previously shown that chronic and developmental exposure to BPA is associated with increased prostate cancer (PCa) risk in human and animal models. Here, we examine whether exposure of PCa cells (LNCaP, C4-2) to low-dose BPA and its structural analogues (BPS, BPF, BPAF, TBBPA, DMBPA and TMBPA) affects centrosome amplification (CA), a hallmark of cancer initiation and progression...
February 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/27990353/effect-of-dihydrotestosterone-on-the-expression-of-mucin-1-and-the-activity-of-wnt-signaling-in-mouse-corneal-epithelial-cells
#9
Li Qin, Cheng Pei, Qian-Yan Kang, Zhao Liu, Li Li
AIM: To explore the effects of the androgen dihydrotestosterone on the expression of mucin 1 (MUC1) and the activity of Wnt signaling in mouse corneal epithelial cells. METHODS: Primary mouse corneal epithelial cells were isolated from the corneas of BALB/c mice. Quantitative real-time polymerase chain reaction, immunofluorescence and Western blot analysis were used to quantify the differential expression of selected genes. The androgen receptor was silenced by transfecting cells with androgen receptor shRNAs...
2016: International Journal of Ophthalmology
https://www.readbyqxmd.com/read/27799360/androgen-receptor-signaling-in-castration-resistant-prostate-cancer-a-lesson-in-persistence
#10
Isabel Coutinho, Tanya Day, Wayne D Tilley, Luke A Selth
The androgen receptor (AR) signaling axis drives all stages of prostate cancer, including the lethal, drug-resistant form of the disease termed castration resistant prostate cancer (CRPC), which arises following failure of androgen deprivation therapy (ADT). Persistent AR activity in spite of ADT and the second-generation AR-targeting agents enzalutamide and abiraterone is achieved in many cases via direct alterations to the AR. Indeed, the role of AR in prostate cancer represents an archetype of therapy-mediated selection pressure and oncogene addiction...
October 31, 2016: Endocrine-related Cancer
https://www.readbyqxmd.com/read/27749325/androgen-receptor-and-beyond-targeting-androgen-signaling-in-castration-resistant-prostate-cancer
#11
Zachery R Reichert, Maha Hussain
The development of metastatic castration-resistant prostate cancer (mCRPC) signals the terminal disease phase. The preceding hormone-dependent disease setting is effectively managed with androgen deprivation therapy. This foundation of treatment has a high rate of biochemical and clinical response and meaningful clinical benefit but is finite in duration as most cancers will progress to castration resistance. Historically, treatment for mCRPC entailed androgen receptor (AR) inhibitors (nilutamide, flutamide, bicalutamide), nonspecific steroidal biosynthesis inhibitors (ketoconazole, itraconazole), steroids (prednisone, diethylstilbesterol, dexamethasone), or palliative chemotherapy (mitoxantrone, estramustine), but none of these strategies impacted survival...
September 2016: Cancer Journal
https://www.readbyqxmd.com/read/27705939/the-andean-anticancer-herbal-product-birm-causes-destabilization-of-androgen-receptor-and-induces-caspase-8-mediated-apoptosis-in-prostate-cancer
#12
Nagarajarao Shamaladevi, Shinako Araki, Dominic A Lyn, Rajnikanth Ayyathurai, Jie Gao, Vinata B Lokeshwar, Hugo Navarrete, Bal L Lokeshwar
BIRM is an anticancer herbal formulation from Ecuador. Previous study established its antitumor and antimetastatic activity against prostate cancer models. The activity of BIRM against human prostate cancer (PCa) cells was investigated to uncover its mechanism of antitumor activity. In androgen receptor (AR)-expressing PCa cells BIRM was 2.5-fold (250%) more cytotoxic in presence of androgen (DHT) compared to cells grown in the absence of DHT. In AR-positive cells (LAPC-4 and LNCaP) BIRM caused a dose and time-dependent down-regulation of AR and increased apoptosis...
October 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27684650/androgen-receptor-involvement-in-rat-amelogenesis-an-additional-way-for-endocrine-disrupting-chemicals-to-affect-enamel-synthesis
#13
Katia Jedeon, Sophia Loiodice, Khaled Salhi, Manon Le Normand, Sophia Houari, Jessica Chaloyard, Ariane Berdal, Sylvie Babajko
Endocrine-disrupting chemicals (EDCs) that interfere with the steroid axis can affect amelogenesis, leading to enamel hypomineralization similar to that of molar incisor hypomineralization, a recently described enamel disease. We investigated the sex steroid receptors that may mediate the effects of EDCs during rat amelogenesis. The expression of androgen receptor (AR), estrogen receptor (ER)-α, and progesterone receptor was dependent on the stage of ameloblast differentiation, whereas ERβ remained undetectable...
September 29, 2016: Endocrinology
https://www.readbyqxmd.com/read/27622605/lentivirus-mediated-p21-waf-1-short-hairpin-rna-enhances-the-cytotoxic-effects-and-replicative-potential-of-a-bladder-cancer-specific-oncolytic-adenovirus-in-vitro
#14
Jie Shi, Shengjun Fu, Li Wang, Yan Tao, Ronald Rodriguez, Zhiping Wang
Our previous work confirmed that the bladder cancer-specific oncolytic adenovirus Ad/PSCAE/UPII/E1A could selectively replicate in bladder cancer cells, thus causing specific tumor cell lysis. The replicative potential is a crucial factor in determining the therapeutic efficacy of oncolytic adenoviruses. However, viral replication is attenuated by the low-activity promoter that we used, thus compromising viral cytotoxicity. In this study, we investigated the effect of the cell cycle-dependent kinase inhibitor p21/Waf-1 on an adenovirus...
January 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/27569375/neuroprotective-effects-of-testosterone-metabolites-and-dependency-on-receptor-action-on-the-morphology-of-somatic-motoneurons-following-the-death-of-neighboring-motoneurons
#15
Yi Cai, Cory Chew, Fernando Muñoz, Dale R Sengelaub
Partial depletion of spinal motoneuron populations induces dendritic atrophy in neighboring motoneurons, and treatment with testosterone is neuroprotective, attenuating induced dendritic atrophy. In this study we examined whether the protective effects of testosterone could be mediated via its androgenic or estrogenic metabolites. Furthermore, to assess whether these neuroprotective effects were mediated through steroid hormone receptors, we used receptor antagonists to attempt to prevent the neuroprotective effects of hormones after partial motoneuron depletion...
August 29, 2016: Developmental Neurobiology
https://www.readbyqxmd.com/read/27557496/dual-targeting-of-androgen-receptor-and-mtorc1-by-salinomycin-in-prostate-cancer
#16
Nooshin Mirkheshti, Sulgi Park, Shoulei Jiang, Jodie Cropper, Sherry L Werner, Chung S Song, Bandana Chatterjee
Androgen receptor (AR) and PI3K/AKT/mTORC1 are major survival signals that drive prostate cancer to a lethal disease. Reciprocal activation of these oncogenic pathways from negative cross talks contributes to low/limited success of pathway-selective inhibitors in curbing prostate cancer progression. We report that the antibiotic salinomycin, a cancer stem cell blocker, is a dual-acting AR and mTORC1 inhibitor, inhibiting PTEN-deficient castration-sensitive and castration-resistant prostate cancer in culture and xenograft tumors...
September 20, 2016: Oncotarget
https://www.readbyqxmd.com/read/27411995/-metastatic-castration-resistant-prostate-cancer-clinical-data-new-treatment-options-and-therapy-monitoring
#17
K Miller, P Albers, R Eichenauer, G Geiges, M-O Grimm, F König, G Mickisch, D Pfister, C Schwentner, H Suttmann, S Zastrow
Therapies currently available in Germany for metastatic castration-resistant prostate cancer (mCRPC) include docetaxel, cabazitaxel, abiraterone acetate, enzalutamide and radium-223, all of which offer a potential survival benefit that adds up in their sequential application to a significant overall survival benefit. However, the optimal sequencing of these agents is still unclear. In the absence of evidence, treatment selection is based on the particular situation and on comorbid conditions of each individual patient...
September 2016: Der Urologe. Ausg. A
https://www.readbyqxmd.com/read/27338375/tumor-necrosis-factor-related-apoptosis-inducing-ligand-induced-apoptosis-in-prostate-cancer-cells-after-treatment-with-xanthohumol-a-natural-compound-present-in-humulus-lupulus-l
#18
Małgorzata Kłósek, Anna Mertas, Wojciech Król, Dagmara Jaworska, Jan Szymszal, Ewelina Szliszka
TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) is an endogenous ligand, which plays role in immune surveillance and anti-tumor immunity. It has ability to selectively kill tumor cells showing no toxicity to normal cells. We tested the apoptotic and cytotoxic activities of xanthohumol, a prenylated chalcone found in Humulus lupulus on androgen-sensitive human prostate adenocarcinoma cells (LNCaP) in combination with TRAIL. Cytotoxicity was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide tetrazolium reduction assay (MTT) and lactate dehydrogenase assay (LDH)...
June 22, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27322458/co-targeting-hexokinase-2-mediated-warburg-effect-and-ulk1-dependent-autophagy-suppresses-tumor-growth-of-pten-and-tp53-deficiency-driven-castration-resistant-prostate-cancer
#19
Lei Wang, Ji Wang, Hua Xiong, Fengxia Wu, Tian Lan, Yingjie Zhang, Xiaolan Guo, Huanan Wang, Mohammad Saleem, Cheng Jiang, Junxuan Lu, Yibin Deng
Currently, no therapeutic options exist for castration-resistant prostate cancer (CRPC) patients who have developed resistance to the second generation anti-androgen receptor (AR) axis therapy. Here we report that co-deletion of Pten and p53 in murine prostate epithelium, often observed in human CRPC, leads to AR-independent CRPC and thus confers de novo resistance to second generation androgen deprivation therapy (ADT) in multiple independent yet complementary preclinical mouse models. In contrast, mechanism-driven co-targeting hexokinase 2 (HK2)-mediated Warburg effect with 2-deoxyglucose (2-DG) and ULK1-dependent autophagy with chloroquine (CQ) selectively kills cancer cells through intrinsic apoptosis to cause tumor regression in xenograft, leads to a near-complete tumor suppression and remarkably extends survival in Pten-/p53-deficiency-driven CRPC mouse model...
May 2016: EBioMedicine
https://www.readbyqxmd.com/read/27222100/increased-expression-and-activity-of-p75ntr-are-crucial-events-in-azacitidine-induced-cell-death-in-prostate-cancer
#20
Giovanni Luca Gravina, Francesco Marampon, Patrizia Sanità, Andrea Mancini, Alessandro Colapietro, Luca Scarsella, Ana Jitariuc, Leda Biordi, Corrado Ficorella, Claudio Festuccia
The high affinity nerve growth factor (NGF) NGF receptor, p75NTR, is a member of the tumor necrosis factor (TNF) receptor superfamily that shares a conserved intracellular death domain capable of inducing apoptosis and suppressing growth in prostate epithelial cells. Expression of this receptor is lost as prostate cancer progresses and is minimal in established prostate cancer cell lines. We aimed to verify the role of p75NTR in the azacitidine-mediated antitumor effects on 22Rv1 and PC3 androgen-independent prostate cancer cells...
July 2016: Oncology Reports
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