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Androgen related genes

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https://www.readbyqxmd.com/read/28415728/lipid-degradation-promotes-prostate-cancer-cell-survival
#1
Harri M Itkonen, Michael Brown, Alfonso Urbanucci, Gregory Tredwell, Chung Ho Lau, Stefan Barfeld, Claire Hart, Ingrid J Guldvik, Mandeep Takhar, Hannelore V Heemers, Nicholas Erho, Katarzyna Bloch, Elai Davicioni, Rita Derua, Etienne Waelkens, James L Mohler, Noel Clarke, Johan V Swinnen, Hector C Keun, Ole P Rekvig, Ian G Mills
Prostate cancer is the most common male cancer and androgen receptor (AR) is the major driver of the disease. Here we show that Enoyl-CoA delta isomerase 2 (ECI2) is a novel AR-target that promotes prostate cancer cell survival. Increased ECI2 expression predicts mortality in prostate cancer patients (p = 0.0086). ECI2 encodes for an enzyme involved in lipid metabolism, and we use multiple metabolite profiling platforms and RNA-seq to show that inhibition of ECI2 expression leads to decreased glucose utilization, accumulation of fatty acids and down-regulation of cell cycle related genes...
March 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28385422/compensatory-response-of-fathead-minnow-larvae-following-a-pulsed-in-situ-exposure-to-a-seasonal-agricultural-runoff-event
#2
Jonathan M Ali, Jodi L Sangster, Daniel D Snow, Shannon L Bartelt-Hunt, Alan S Kolok
Agriculturally-dominated waterways such as those found throughout the Midwestern United States often experience seasonal pulses of agrichemical contaminants which pose a potential hazard to aquatic organisms at varying life stages. The objective of this study was to characterize the developmental plasticity of fathead minnow larvae in a natural environment subject to a seasonal episodic perturbation in the form of a complex mixture of agricultural stressors. Fathead minnow larvae were maintained at the Elkhorn River Research Station for a 28-d in situ exposure to an agrichemical pulse event...
April 3, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28379958/il-15-regulates-migration-invasion-angiogenesis-and-genes-associated-with-lipid-metabolism-and-inflammation-in-prostate-cancer
#3
Krizia Rohena-Rivera, María M Sánchez-Vázquez, Diana A Aponte-Colón, Ingrid S Forestier-Román, Mario E Quintero-Aguiló, Magaly Martínez-Ferrer
Prostate cancer (PCa) is the most commonly diagnosed non-cutaneous cancer. In the United States it is second leading cause of cancer related deaths in men. PCa is often treated via radical prostatectomy (RP). However, 15-30% of the patients develop biochemical recurrence (i.e. increased serum prostate specific antigen (PSA) levels). Interleukin-15 (IL-15) is a secreted cytokine found over expressed in patients with recurrence-free survival after RP. In our study, we aim to determine the role of IL-15 in PCa using in vitro and in vivo models, and gene expression analysis...
2017: PloS One
https://www.readbyqxmd.com/read/28341248/abnormal-lipid-lipoprotein-metabolism-and-high-plasma-testosterone-levels-in-male-but-not-female-aromatase-knockout-mice
#4
Akiko Amano, Yoshitaka Kondo, Yoshihiro Noda, Mitsuhiro Ohta, Noriaki Kawanishi, Shuichi Machida, Kazuteru Mitsuhashi, Takafumi Senmaru, Michiaki Fukui, Osamu Takaoka, Taisuke Mori, Jo Kitawaki, Masafumi Ono, Toshiji Saibara, Hiroshi Obayashi, Akihito Ishigami
Sex steroid hormones, such as estrogen and testosterone, are believed to play important roles in lipid metabolism. To elucidate the effects of estrogen depletion on lipid metabolism in male and female mice, we used aromatase-knockout (ArKO) mice, in which Cyp19 gene disruption prevented estrogen synthesis in vivo. These mice were divided into the following 4 groups: male and female ArKO mice and male and female wild-type (WT) mice. These mice were fed a normal-fat diet (13.6% fat) ad libitum. At 159 days after birth, the mice were tested for liver and plasma lipid content and hepatic hormone receptor- and lipid/lipoprotein metabolism-related gene expression...
March 22, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28336462/the-molecular-mechanisms-of-androgen-receptor-in-nephrolithiasis
#5
Ziyu Fang, Yonghan Peng, Ling Li, Min Liu, Zeyu Wang, Shaoxiong Ming, Wenhui Zhang, Xiaofeng Gao
OBJECTIVES: This study aimed to investigate the molecular mechanisms of androgen receptor (AR) in nephrolithiasis. METHODS: Human kidney 2(HK-2) cells were transfected with Lentiviruses expressing AR (DEC-AR), shRNA targeting AR (sh-AR) or the empty vector control using the pLEX lentiviral vector system. The expression levels of AR were measured by qRT-PCR at 72h postinfection, and cells under different treatments were collected for microarray analysis. Differentially expressed genes (DEGs) were identified using Student's t-test...
June 15, 2017: Gene
https://www.readbyqxmd.com/read/28336389/metformin-ameliorates-uterine-defects-in-a-rat-model-of-polycystic-ovary-syndrome
#6
Yuehui Zhang, Min Hu, Fanci Meng, Xiaoyan Sun, Hongfei Xu, Jiao Zhang, Peng Cui, Njomeza Morina, Xin Li, Wei Li, Xiao-Ke Wu, Mats Brännström, Ruijin Shao, Håkan Billig
Adult rats treated concomitantly with insulin and human chorionic gonadotropin exhibit endocrine, metabolic, and reproductive abnormalities that are very similar to those observed in polycystic ovary syndrome (PCOS) patients. In this study, we used this rat model to assess the effects of metformin on PCOS-related uterine dysfunction. In addition to reducing androgen levels, improving insulin sensitivity, and correcting the reproductive cycle, metformin treatment induced morphological changes in the PCOS-like uterus...
March 18, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28334513/the-number-of-cag-and-ggn-triplet-repeats-in-the-androgen-receptor-gene-exert-combinatorial-effect-on-hormonal-and-sperm-parameters-in-young-men
#7
M Grigorova, M Punab, T Kahre, M Ivandi, N Tõnisson, O Poolamets, V Vihljajev, B Žilaitienė, J Erenpreiss, V Matulevičius, M Laan
Androgen receptor (AR) is a transcription factor that is activated upon binding to testosterone (T) and is implicated in regulating the expression of reproduction-related genes. The human AR gene (Xq11-12) spans 186,588 bp and eight exons. N-terminal transactivation domain of the encoded AR protein harbours two polymorphic stretches of identical amino acids, a polyglutamine tract (encoded by 8-37 CAG-repeats) and a polyglycine tract (encoded by 10-30 GGN-repeats). We set forward to analyse independent and combinatory effects of the length of these repetitive tracts on male reproductive hormones, testicular and sperm parameters in a population-based cohort of Baltic young men (n = 974; aged 20...
May 2017: Andrology
https://www.readbyqxmd.com/read/28334178/inter-regional-variations-in-gene-expression-and-age-related-cortical-thinning-in-the-adolescent-brain
#8
Angelita Pui-Yee Wong, Leon French, Gabriel Leonard, Michel Perron, G Bruce Pike, Louis Richer, Suzanne Veillette, Zdenka Pausova, Tomáš Paus
Age-related decreases in cortical thickness observed during adolescence may be related to fluctuations in sex and stress hormones. We examine this possibility by relating inter-regional variations in age-related cortical thinning (data from the Saguenay Youth Study) to inter-regional variations in expression levels of relevant genes (data from the Allen Human Brain Atlas); we focus on genes coding for glucocorticoid receptor (NR3C1), androgen receptor (AR), progesterone receptor (PGR), and estrogen receptors (ESR1 and ESR2)...
February 25, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28329024/toward-developing-recombinant-gonadotropin-based-hormone-therapies-for-increasing-fertility-in-the-flatfish-senegalese-sole
#9
François Chauvigné, Judith Ollé, Wendy González, Neil Duncan, Ignacio Giménez, Joan Cerdà
Captive flatfishes, such as the Senegalese sole, typically produce very low volumes of sperm. This situation is particularly prevalent in the first generation (F1) of reared sole males, which limits the development of artificial fertilization methods and the implementation of selective breeding programs. In this study, we investigated whether combined treatments with homologous recombinant follicle-stimulating (rFsh) and luteinizing (rLh) hormones, produced in a mammalian host system, could stimulate spermatogenesis and enhance sperm production in Senegalese sole F1 males...
2017: PloS One
https://www.readbyqxmd.com/read/28322549/vitamin-c-modulates-the-immunotoxic-effect-of-17%C3%AE-methyltestosterone-in-nile-tilapia
#10
Haitham G Abo-Al-Ela, Abeer F El-Nahas, Shawky Mahmoud, Essam M Ibrahim
The synthetic androgen 17α-methyltestosterone (MT) is profusely used and practically needed in the production of all-male Nile tilapia fry; however, such androgenic hormones badly disrupt the immune system. This study aimed to alleviate or counteract the immunotoxic effect of MT using vitamin C (ascorbic acid or vit C). Our results show that the highest phagocytic activity (PA), phagocytic index (PI), and lysozyme activity were detected in the vit C group and the MT plus vit C group. Furthermore, PA and PI were significantly suppressed, but lysozyme activity was stronger in the MT group than in the control...
March 28, 2017: Biochemistry
https://www.readbyqxmd.com/read/28301631/androgen-receptor-function-and-androgen-receptor-targeted-therapies-in-breast-cancer-a-review
#11
Miho Kono, Takeo Fujii, Bora Lim, Meghan Sri Karuturi, Debasish Tripathy, Naoto T Ueno
Importance: The androgen receptor (AR) pathway is emerging as a potential therapeutic target in breast cancer. To date, AR-targeted drugs have been approved only for treatment of prostate cancer; however, AR-targeted treatment for breast cancer is an area of active investigation. Through review of preclinical studies, retrospective clinical studies, and clinical trials, we examined the biology of AR and AR-related pathways, the potential for AR-targeted therapies in breast cancer, and potential biomarkers for AR-targeted treatments...
March 16, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28289210/phosphorylation-induced-conformational-dynamics-in-an-intrinsically-disordered-protein-and-potential-role-in-phenotypic-heterogeneity
#12
Prakash Kulkarni, Mohit Kumar Jolly, Dongya Jia, Steven M Mooney, Ajay Bhargava, Luciane T Kagohara, Yihong Chen, Pengyu Hao, Yanan He, Robert W Veltri, Alexander Grishaev, Keith Weninger, Herbert Levine, John Orban
Intrinsically disordered proteins (IDPs) that lack a unique 3D structure and comprise a large fraction of the human proteome play important roles in numerous cellular functions. Prostate-Associated Gene 4 (PAGE4) is an IDP that acts as a potentiator of the Activator Protein-1 (AP-1) transcription factor. Homeodomain-Interacting Protein Kinase 1 (HIPK1) phosphorylates PAGE4 at S9 and T51, but only T51 is critical for its activity. Here, we identify a second kinase, CDC-Like Kinase 2 (CLK2), which acts on PAGE4 and hyperphosphorylates it at multiple S/T residues, including S9 and T51...
March 28, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28277126/alteration-in-follistatin-gene-expression-detected-in-prenatally-androgenized-rats
#13
Marziyeh Salehi Jahromi, Fahimeh Ramezani Tehrani, Jennifer W Hill, Mahsa Noroozzadeh, Maryam Zarkesh, Asghar Ghasemi, Azita Zadeh-Vakili
Impaired ovarian follicle development, the hallmark of polycystic ovarian syndrome (PCOS), is believed to be due to the changes in expression of related genes such as follistatin (FST). Expression of FST gene and methylation level of its promoter in theca cells from adult female rats, prenatally exposed to androgen excess, during different phases of the estrus cycle was determined and compared with controls. Eight pregnant Wistar rats (experimental group) were treated by subcutaneous injection of 5 mg free testosterone on day 20 of pregnancy, while controls (n = 8) received 500 ml solvent...
February 26, 2017: Gynecological Endocrinology
https://www.readbyqxmd.com/read/28270124/cyproterone-acetate-enhances-trail-induced-androgen-independent-prostate-cancer-cell-apoptosis-via-up-regulation-of-death-receptor-5
#14
Linjie Chen, Dennis W Wolff, Yan Xie, Ming-Fong Lin, Yaping Tu
BACKGROUND: Virtually all prostate cancer deaths occur due to obtaining the castration-resistant phenotype after prostate cancer cells escaped from apoptosis and/or growth suppression initially induced by androgen receptor blockade. TNF-related apoptosis-inducing ligand (TRAIL) was an attractive cancer therapeutic agent due to its minimal toxicity to normal cells and remarkable apoptotic activity in tumor cells. However, most localized cancers including prostate cancer are resistant to TRAIL-induced apoptosis, thereby creating a therapeutic challenge of inducing TRAIL sensitivity in cancer cells...
March 7, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28259476/treatment-outcomes-and-tumor-loss-of-heterozygosity-in-germline-dna-repair-deficient-prostate-cancer
#15
Matti Annala, Werner J Struss, Evan W Warner, Kevin Beja, Gillian Vandekerkhove, Amanda Wong, Daniel Khalaf, Irma-Liisa Seppälä, Alan So, Gregory Lo, Rahul Aggarwal, Eric J Small, Matti Nykter, Martin E Gleave, Kim N Chi, Alexander W Wyatt
BACKGROUND: Germline mutations in DNA repair genes were recently reported in 8-12% of patients with metastatic castration-resistant prostate cancer (mCRPC). It is unknown whether these mutations associate with differential response to androgen receptor (AR)-directed therapy. OBJECTIVE: To determine the clinical response of mCRPC patients with germline DNA repair defects to AR-directed therapies and to establish whether biallelic DNA repair gene loss is detectable in matched circulating tumor DNA (ctDNA)...
March 1, 2017: European Urology
https://www.readbyqxmd.com/read/28257035/rnase-l-suppresses-androgen-receptor-signaling-cell-migration-and-matrix-metalloproteinase-activity-in-prostate-cancer-cells
#16
Shubham Dayal, Jun Zhou, Praveen Manivannan, Mohammad Adnan Siddiqui, Omaima Farid Ahmad, Matthew Clark, Sahezeel Awadia, Rafael Garcia-Mata, Lirim Shemshedini, Krishnamurthy Malathi
The interferon antiviral pathways and prostate cancer genetics converge on a regulated endoribonuclease, RNase L. Positional cloning and linkage studies mapped Hereditary Prostate Cancer 1 (HPC1) to RNASEL. To date, there is no correlation of viral infections with prostate cancer, suggesting that RNase L may play additional roles in tumor suppression. Here, we demonstrate a role of RNase L as a suppressor of androgen receptor (AR) signaling, cell migration and matrix metalloproteinase activity. Using RNase L mutants, we show that its nucleolytic activity is dispensable for both AR signaling and migration...
March 1, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28235401/expression-of-socs1-and-the-downstream-targets-of-its-putative-tumor-suppressor-functions-in-prostate-cancer
#17
Martin Chevrier, Diwakar Bobbala, Alberto Villalobos-Hernandez, Md Gulam Musawwir Khan, Sheela Ramanathan, Caroline Saucier, Gerardo Ferbeyre, Sameh Geha, Subburaj Ilangumaran
BACKGROUND: Suppressor of cytokine signaling 1 (SOCS1) is considered a tumor suppressor due to frequent epigenetic and micro-RNA-mediated repression of its gene expression in diverse cancers. In prostate cancer (PCa), elevated expression of miR-30d that targets SOCS1 mRNA is associated with increased risk of disease recurrence. SOCS1 can mediate its tumor suppressor functions by diverse mechanisms such as inhibiting the JAK-STAT signaling pathway, promoting the tumor suppressor functions of p53, attenuating MET receptor tyrosine kinase signaling and blocking the oncogenic potential of the cell cycle inhibitor p21(CIP1) (p21)...
February 24, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28215832/variation-in-the-clinical-and-genetic-evaluation-of-undervirilized-boys-with-bifid-scrotum-and-hypospadias
#18
J M Swartz, R Ciarlo, E Denhoff, A Abrha, D A Diamond, J N Hirschhorn, Y-M Chan
BACKGROUND: Bifid scrotum and hypospadias can be signs of undervirilization, yet boys presenting with these findings often do not undergo genetic evaluation. In some cases, identifying an underlying genetic diagnosis can help to optimize clinical care and improve guidance given to patients and families. OBJECTIVES: The aim of this study was to characterize current practice for genetic evaluation of patients with bifid scrotum, and to identify approaches with a good diagnostic yield...
January 30, 2017: Journal of Pediatric Urology
https://www.readbyqxmd.com/read/28213303/diethylstilbestrol-flutamide-and-their-combination-impaired-the-spermatogenesis-of-male-adult-zebrafish-through-disrupting-hpg-axis-meiosis-and-apoptosis
#19
Pan Yin, Ying-Wen Li, Qi-Liang Chen, Zhi-Hao Liu
Both diethylstilbestrol (DES, an environmental estrogen) and flutamide (FLU, an anti-androgen) are found to impair spermatogenesis by disrupting hypothalamic-pituitary-gonadal (HPG) axis and altering androgen levels through different mechanisms/modes of action in fish with poorly understood underlying mechanisms. Furthermore, it is not known whether and how a combined exposure of DES and FLU has a stronger effect than the compounds alone. In this study, male zebrafish adults were exposed to DES, FLU and their combination (DES+FLU) for 30days, and their effects on histological structure and sperm count in testis, androgen level in plasma, as well as the mRNA levels of genes involved in HPG axis, meiotic regulation and apoptosis were analyzed...
April 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/28192399/c-met-mir-130b-axis-as-novel-mechanism-and-biomarker-for-castration-resistance-state-acquisition
#20
A Cannistraci, G Federici, A Addario, A L Di Pace, L Grassi, G Muto, D Collura, M Signore, L De Salvo, S Sentinelli, G Simone, M Costantini, S Nanni, A Farsetti, V Coppola, R De Maria, D Bonci
Although a significant subset of prostate tumors remain indolent during the entire life, the advanced forms are still one of the leading cause of cancer-related death. There are not reliable markers distinguishing indolent from aggressive forms. Here we highlighted a new molecular circuitry involving microRNA and coding genes promoting cancer progression and castration resistance. Our preclinical and clinical data demonstrated that c-Met activation increases miR-130b levels, inhibits androgen receptor expression, promotes cancer spreading and resistance to hormone ablation therapy...
February 13, 2017: Oncogene
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