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Androgen related genes

Sundhar Ramalingam, Adva Eisenberg, Wen Chi Foo, Jennifer Freedman, Andrew J Armstrong, Larry G Moss, Michael R Harrison
Here we present, to the best of our knowledge, the first case of a paraneoplastic Cushing's syndrome (hypercortisolism) resulting from treatment-related neuroendocrine prostate cancer - a highly aggressive and difficult disease to treat. A 51-year-old man was started on androgen deprivation therapy after presenting with metastatic prostate cancer, characterized by diffuse osseous metastasis. Shortly thereafter, he developed progressive disease with biopsy proven neuroendocrine prostate cancer as well as symptoms of increased skin pigmentation, hypokalemia, hypertension, hyperglycemia and profound weakness, consistent with ectopic Cushing's syndrome...
October 21, 2016: International Journal of Urology: Official Journal of the Japanese Urological Association
Milan S Geybels, Karen D McCloskey, Ian G Mills, Janet L Stanford
BACKGROUND: Calcium channel blockers (CCBs) may affect prostate cancer (PCa) growth by various mechanisms including those related to androgens. The fusion of the androgen-regulated gene TMPRSS2 and the oncogene ERG (TMPRSS2:ERG or T2E) is common in PCa, and prostate tumors that harbor the gene fusion are believed to represent a distinct disease subtype. We studied the association of CCB use with the risk of PCa, and molecular subtypes of PCa defined by T2E status. METHODS: Participants were residents of King County, Washington, recruited for population-based case-control studies (1993-1996 or 2002-2005)...
October 18, 2016: Prostate
Liming Wang, L Zhu, R Luan, L Wang, J Fu, X Wang, L Sui
Dilated cardiomyopathy (DCM) is characterized by ventricular dilatation, and it is a common cause of heart failure and cardiac transplantation. This study aimed to explore potential DCM-related genes and their underlying regulatory mechanism using methods of bioinformatics. The gene expression profiles of GSE3586 were downloaded from Gene Expression Omnibus database, including 15 normal samples and 13 DCM samples. The differentially expressed genes (DEGs) were identified between normal and DCM samples using Limma package in R language...
October 10, 2016: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
Jane Date C Hon, Baljit Singh, Aysegul Sahin, Gang Du, Jinhua Wang, Vincent Y Wang, Fang-Ming Deng, David Y Zhang, Marie E Monaco, Peng Lee
Treatment protocols for breast cancer depend predominantly on receptor status with respect to estrogen (estrogen receptor alpha), progesterone (progesterone receptor) and human epidermal growth factor [human epidermal growth factor receptor 2 (HER2)]. The presence of one or more of these receptors suggests that a treatment targeting these pathways might be effective, while the absence of, or in the case of HER2, lack of overexpression of, all of these receptors, termed triple negative breast cancer (TNBC), indicates a need for the more toxic chemotherapy...
2016: American Journal of Cancer Research
Hye-Eun Choi, Ji-Sun Shin, Dong-Gyu Leem, Soo-Dong Kim, Won-Jea Cho, Kyung-Tae Lee
Previously, we reported that 6-(3,4-dihydro-1H-isoquinolin-2-yl)-N-(6-methylpyridin-2-yl) nicotinamide (DIMN) analogues inhibited the growth of prostate cancer cells as an anti-androgenic compound. In the present study, we evaluated cytotoxic effects of these DIMN derivatives and found that DIMN-26 most potently inhibited the proliferation of the LNCap-LN3 androgen-dependent and DU145 androgen-independent prostate cancer cells through induction of G2/M phase cell cycle arrest and subsequent apoptosis. The G2/M phase arrest was found due to increases in the activation of cdc2 (also known as cyclin-dependent kinase 1, CDK1)/cyclin B1 complex...
October 5, 2016: Chemico-biological Interactions
Rebecca Milsk, Jenna E Cavallin, Elizabeth J Durhan, Kathleen M Jensen, Michael D Kahl, Elizabeth A Makynen, Dalma Martinović-Weigelt, Nathan Mueller, Anthony Schroeder, Daniel L Villeneuve, Gerald T Ankley
The aim of this study was to investigate temporal changes in the hypothalamic-pituitary-gonadal (HPG) axis of fathead minnows (Pimephales promelas) treated with the model androgen receptor (AR) antagonist flutamide. Reproductively-mature fish were exposed in a flow-through test to analytically-confirmed concentrations of either 50 or 500μg flutamide/L for 8 d, followed by an 8-d recovery period in clean water. Fish were sampled at 1, 2, 4 and 8days during each phase of the experiment. Flutamide (500μg/L) caused significant reductions in relative gonad size of the females on day 8 of the exposure and day 1 of the recovery, and reduced expression of secondary sex characteristics in males during the exposure phase of the experiment...
October 1, 2016: Aquatic Toxicology
Christoph Eisenegger, Robert Kumsta, Michael Naef, Jörg Gromoll, Markus Heinrichs
A contribution to a special issue on Hormones and Human Competition Studies in non-human animals and humans have demonstrated the important role of testosterone in competitive interactions. Here, we investigated whether endogenous testosterone levels predict the decision to compete, in a design excluding spite as a motive underlying competitiveness. In a laboratory experiment with real monetary incentives, 181 men solved arithmetic problems, first under a noncompetitive piece rate, followed by a competition incentive scheme...
October 1, 2016: Hormones and Behavior
Masaru Koido, Junko Sakurai, Satomi Tsukahara, Yuri Tani, Akihiro Tomida
Prostate transmembrane protein, androgen induced 1 (PMEPA1) is highly expressed in various solid tumors and is known to play important roles in the transforming growth factor-β (TGF-β) signaling pathway. Here, we demonstrate a novel relationship between PMEPA1 and hypoxia, a common microenvironmental stress condition in solid tumors. We showed that induction of PMEPA1 expression occurred during hypoxia in a manner dependent on both TGF-β signaling and hypoxia-inducible factor-1 (HIF-1) pathways. Furthermore, overexpression and knockdown experiments revealed that PMEPA1 enhanced HIF-1 transcription activity...
October 28, 2016: Biochemical and Biophysical Research Communications
H Suzuki, S Matsushita, K Suzuki, G Yamada
Androgen is an essential factor involved in masculinization of external genitalia. Failure of the exposure to 5α-dihydrotestosterone (DHT) causes a hypoplastic penile size and urethral abnormality. The main pathology of hypospadias is defective urethral closure on the ventral side of the penis. Hormone-dependent genes are suggested as the causative factors. However, the detailed mechanisms of DHT functions on urethral tube formation remain unknown. Androgen is both a positive and negative regulator of cell proliferation...
October 1, 2016: Andrology
Katharina R Beck, Tanja J Sommer, Daniela Schuster, Alex Odermatt
The incidence of immune-related diseases increased over the last years in industrialized countries, suggesting a contribution of environmental factors. Impaired glucocorticoid action has been associated with immune disorders. Thus, there is an increasing interest to identify chemicals disrupting glucocorticoid action. The widely used flame retardant tetrabromobisphenol A (TBBPA) was reported earlier to potently inhibit glucocorticoid receptor (GR) and moderately androgen receptor (AR) activity in yeast-based reporter gene assays...
September 28, 2016: Toxicology
Shubo Jin, Dajiang Sun, Qingkai Xi, Xiaoli Dong, Dan Song, Hongtuo Fu, Ying Zhang
Kisspeptin plays an important role in the reproduction and onset of puberty in vertebrates through stimulation of gonadotropin-releasing hormone (GnRH). However, the mechanisms whereby kisspeptin-related genes regulate sexual differentiation in teleosts are poorly understood. We aimed to study the relationship between the hypothalamus-pituitary-gonad (HPG) axis and sexual differentiation in relation to kisspeptin in the sturgeon Acipenser schrenckii. We performed comparative transcriptomic analysis of the brains of sturgeons treated with KISS1-10 during the gonadal sex-differentiation-sensitive period (170-210days post-hatching (dph)) using an Illumina sequencing platform...
September 26, 2016: Gene
Rabab H Sayed, Muhammed A Saad, Ayman E El-Sahar
Serotonin level plays a role in suppressing the pathological findings of benign prostatic hyperplasia (BPH). Thus a new selective serotonin reuptake inhibitor, dapoxetine was used to test its ability to ameliorate the pathological changes in the rat prostate. A dose response curve was constructed between the dose of dapoxetine and prostate weight as well as relative prostate weight, then a 5mg/kg dose was used as a representative dose for dapoxetine administration. Rats were divided into four groups; the control group that received the vehicle; the BPH-induced group received daily s...
September 27, 2016: Toxicology and Applied Pharmacology
P Díaz, H Cardenas, P A Orihuela
We examined whether aqueous extract of Lepidium meyenii (red Maca) could inhibit growth, potentiate apoptotic activity of two anticancer drugs Taxol and 2-methoxyestradiol (2ME) or change mRNA expression for the androgen target genes, androgen receptor (Ar) and prostate-specific antigen (Psa) in the human prostate cancer cell line LNCaP. Red Maca aqueous extract at 0, 10, 20, 40 or 80 μg/ml was added to LNCaP cells, and viability was evaluated by the MTS assay at 24 or 48 hr after treatment. Furthermore, LNCaP cells were treated with 80 μg/ml of red Maca plus Taxol or 2ME 5 μM and viability was assessed 48 hr later...
October 2016: Andrologia
Hong-Yi Zhang, Ya-Dong Ma, Ye Zhang, Jie Cui, Zi-Ming Wang
AIM: To evaluate the expression levels and prognostic significance of autophagy-related markers, UNC-51-like kinase1 (ULK1), Beclin1, microtubule-associated protein light chain 3 (LC3), autophagy-related gene 5 (ATG5) and mitochondrion-associated autophagy inhibitor, LRPPRC, in patients with metastatic prostate cancer (PCa) after androgen deprivation therapy (ADT). METHODS: Expressions of ULK1, Beclin1, LC3, ATG5 and LRPPRC were assessed by immunohistochemical examination in 198 patients with metastatic PCa who were receiving ADT (goserelin and bicalutamide)...
September 27, 2016: Journal of Clinical Pathology
Xiu-Wu Pan, Si-Shun Gan, Jian-Qing Ye, Ying-Hui Fan, Υi Hong, Chuan-Min Chu, Yi Gao, Lin Li, Xi Liu, Lu Chen, Yi Huang, Hong Xu, Ji-Zhong Ren, Lei Yin, Fa-Jun Qu, Hai Huang, Xin-Gang Cui, Dan-Feng Xu
Structural maintenance of chromosome 1 alpha (SMC1A) gene has been reported to be related to tumor development in some types of human cancers. However, the misregulation of SMC1A and its functions in castration-resistant prostate cancer (CRPC) have not been well understood. In the present study, we found that SMC1A was elevated in androgen-independent PCa cell lines PC-3 and DU-145 compared to androgen sensitive LNCap and 22RV1 cells by qPCR and western blot assay. Knockdown of SMC1A inhibited cell growth, colony formation and cell migration abilities of PC-3 and DU145 cells by MTT, colony formation and transwell assays, and affected cell cycle progression in PC-3 and DU145 cells by flow cytometry...
September 19, 2016: International Journal of Oncology
Milan S Geybels, Jonathan L Wright, Marina Bibikova, Brandy Klotzle, Jian-Bing Fan, Shanshan Zhao, Ziding Feng, Elaine A Ostrander, Daniel W Lin, Peter S Nelson, Janet L Stanford
BACKGROUND: Identifying the subset of patients with clinically localized prostate cancer (PCa) at the highest risk of recurrence remains challenging, and better prognostic markers are needed. Gleason score is the best predictor of PCa aggressiveness and prognosis. In the present study, we generated an epigenetic signature based on high versus low Gleason score tumors and evaluated its ability to predict recurrence after radical prostatectomy. METHODS: Genome-wide DNA methylation data from The Cancer Genome Atlas (TCGA; no...
2016: Clinical Epigenetics
Robert J A H Eendebak, Ilpo Huhtaniemi, Stephen R Pye, Tomas Brian Ahern, Terence W O'Neill, Gyorgy Bartfai, Felipe F Casanueva, Mario Maggi, Gianni Forti, Robert D Alston, Aleksander Giwercman, Thang S Han, Krzysztof Kula, Mike Lean, Margus Punab, Neil Pendleton, Brian Keevil, Dirk Vanderschueren, Martin Kenneth Rutter, Gindo Tampubolon, Royston Goodacre, Fredrick C W Wu
CONTEXT: The Androgen Receptor (AR) gene exon 1 CAG repeat length has been proposed to be a determinant of between-individual variations in androgen action in target tissues, which might regulate phenotypic differences of human ageing. However, findings on its phenotypic effects are inconclusive. OBJECTIVE: To assess whether the AR CAG repeat length is associated with longitudinal changes in endpoints which are influenced by testosterone (T) levels in middle-aged and elderly European men...
September 15, 2016: European Journal of Endocrinology
Damien A Leach, Vasilios Panagopoulos, Claire Nash, Charlotte Bevan, Axel A Thomson, Luke A Selth, Grant Buchanan
Androgen receptor (AR) signalling in fibroblasts is important in prostate development and carcinogenesis, and is inversely related to prostate cancer mortality. However, the molecular mechanisms of AR action in fibroblasts and other non-epithelial cell types are largely unknown. The genome-wide DNA binding profile of AR in human prostate fibroblasts was identified by chromatin immunoprecipitation sequencing (ChIP-Seq), and found to be common to other fibroblast lines but disparate from AR cistromes of prostate cancer cells and tissue...
September 12, 2016: Molecular and Cellular Endocrinology
Jeremy A Spool, Sharon A Stevenson, Caroline S Angyal, Lauren V Riters
Animals integrate social information with their internal endocrine state to control the timing of behavior, but how these signals are integrated in the brain is not understood. The medial preoptic area (mPOA) may play an integrative role in the control of courtship behavior, as it receives projections from multiple sensory systems, and is central to the hormonal control of courtship behavior across vertebrates. Additionally, data from many species implicate opioid and dopaminergic systems in the mPOA in the control of male courtship behavior...
September 12, 2016: Hormones and Behavior
Joshua William Smith, Nikki A Ford, Jennifer M Thomas-Ahner, Nancy E Moran, Eric C Bolton, Matthew A Wallig, Steven K Clinton, John W Erdman
β-carotene-15,15'-dioxygenase (BCO1) cleaves dietary carotenoids at the central 15,15' double bond, most notably acting on β-carotene to yield retinal. However, Bco1 disruption also impacts diverse physiologic endpoints independent of dietary carotenoid feeding, including expression of genes controlling androgen metabolism. Using the Bco1(-/-) mouse model, we sought to probe the effects of Bco1 disruption on testicular steroidogenesis, prostatic androgen signaling, and prostatic proliferation. Male wild-type (WT) and Bco1(-/-) mice were raised on carotenoid-free AIN-93G diets before euthanasia between 10-14 weeks of age...
September 14, 2016: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
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