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Androgen related genes

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https://www.readbyqxmd.com/read/29239100/insulin-like-growth-factor-2-expression-in-prostate-cancer-is-regulated-by-specific-promoter-methylation
#1
Stefan Küffer, Tobias Gutting, Djeda Belharazem, Christian Sauer, M S Michel, Alexander Marx, Lutz Trojan, Philipp Ströbel
Deregulation of the Insulin-like Growth Factor (IGF) axis and dysbalance of components of the IGF system as potential therapeutic targets have been described in different tumor types. IGF2 is a major embryonic growth factor and an important activator of IGF signaling. It is regulated by imprinting in a development- and tissue-dependent manner and has been implicated in a broad range of malignancies including prostate cancer (PCa). Loss of imprinting (LOI) usually results in bi-allelic gene expression and increased levels of IGF2...
December 14, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/29237712/receptor-activities-of-persistent-pollutant-serum-mixtures-and-breast-cancer-risk
#2
Maria Wielsøe, Christian Bjerregaard-Olesen, Peder Kern, Eva Cecilie Bonefeld-Jørgensen
Studies on associations between persistent organic pollutants (POPs) and breast cancer risk are inconclusive. The majority of studies have evaluated the effect of single compounds, without considering multiple exposures to and interactions between different POPs. The present study aimed at evaluating breast cancer risk related to combined effects of serum POP mixtures on cellular receptor functions. Data on breast cancer cases (n=77) and controls (n=84) was collected among Greenlandic Inuit women. Serum mixtures of lipophilic POPs (lipPOPs), perfluoroalkyl acids (PFAAs), and dioxin-like POPs were extracted...
December 13, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29233929/single-cell-rna-seq-reveals-a-subpopulation-of-prostate-cancer-cells-with-enhanced-cell-cycle-related-transcription-and-attenuated-androgen-response
#3
Aaron M Horning, Yao Wang, Che-Kuang Lin, Anna D Louie, Rohit R Jadhav, Chia-Nung Hung, Chiou-Miin Wang, Chun-Lin Lin, Nameer B Kirma, Michael A Liss, Addanki P Kumar, LuZhe Sun, Zhijie Liu, Wei-Ting Chao, Qianben Wang, Victor X Jin, Chun-Liang Chen, Tim H-M Huang
Increasing evidence suggests the presence of minor cell subpopulations in prostate cancer that are androgen independent and poised for selection as dominant clones after androgen-deprivation therapy. In this study, we investigated this phenomenon by stratifying cell subpopulations based on transcriptome profiling of 144 single LNCaP prostate cancer cells treated or untreated with androgen after cell cycle synchronization. Model-based clustering of 397 differentially expressed genes identified eight potential subpopulations of LNCaP cells, revealing a previously unappreciable level of cellular heterogeneity to androgen stimulation...
December 12, 2017: Cancer Research
https://www.readbyqxmd.com/read/29228719/levels-of-leydig-cell-autophagy-regulate-the-fertility-of-male-naked-mole-rats
#4
Wenjing Yang, Li Li, Xiaofeng Huang, Guanghan Kan, Lifang Lin, Jishuai Cheng, Chen Xu, Wei Sun, Wei Cong, Shanmin Zhao, Shufang Cui
Fertility is abolished in nonbreeding males in colonies of natal naked mole-rats (NMRs). Although spermatogenesis occurs in both breeding and nonbreeding male NMRs, the mechanisms underlying the differences in fertility between breeders and nonbreeders remain unexplored. In this study, a significant decrease in autophagy was observed in Leydig cells of the testis from nonbreeding male NMRs. This alteration was visualised as a significant decrease in the levels of autophagy-related gene 7 (Atg7), Atg5, microtubule-associated protein 1A/B light chain 3 (LC3-II/I) and the number of autophagosomes and an increase in P62 levels using Western blotting analyses...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29228205/associations-between-polymorphisms-in-genes-related-to-estrogen-metabolism-and-function-and-prostate-cancer-risk-results-from-the-prostate-cancer-prevention-trial
#5
Li Tang, Mary E Platek, Song Yao, Cathee Till, Phyllis J Goodman, Catherine M Tangen, Yue Wu, Elizabeth A Platz, Marian L Neuhouser, Frank Z Stanczyk, Juergen K V Reichardt, Regina M Santella, Ann Hsing, William D Figg, Scott M Lippman, Ian M Thompson, Christine B Ambrosone
Substantial preclinical data suggest estrogen's carcinogenic role in prostate cancer development; however, epidemiological evidence based on circulating estrogen levels is largely null. Compared with circulating estrogen, the intraprostatic estrogen milieu may play a more important role in prostate carcinogenesis. Using a nested case-control design in the Prostate Cancer Prevention Trial (PCPT), we examined associations of genetic variants of genes that are involved in estrogen synthesis, metabolism and function with prostate cancer risk...
December 8, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/29216878/adaptive-phenotype-drives-resistance-to-androgen-deprivation-therapy-in-prostate-cancer
#6
Nicoletta Ferrari, Ilaria Granata, Matteo Capaia, Marina Piccirillo, Mario Rosario Guarracino, Roberta Venè, Antonella Brizzolara, Andrea Petretto, Elvira Inglese, Martina Morini, Simonetta Astigiano, Adriana Agnese Amaro, Francesco Boccardo, Cecilia Balbi, Paola Barboro
BACKGROUND: Prostate cancer (PCa), the second most common cancer affecting men worldwide, shows a broad spectrum of biological and clinical behaviour representing the epiphenomenon of an extreme heterogeneity. Androgen deprivation therapy is the mainstay of treatment for advanced forms but after few years the majority of patients progress to castration-resistant prostate cancer (CRPC), a lethal form that poses considerable therapeutic challenges. METHODS: Western blotting, immunocytochemistry, invasion and reporter assays, and in vivo studies were performed to characterize androgen resistant sublines phenotype in comparison to the parental cell line LNCaP...
December 8, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/29212159/lef1-tfe3-and-ar-are-putative-diagnostic-markers-of-solid-pseudopapillary-neoplasms
#7
Eun Kyung Kim, Mi Jang, Minhee Park, Hoguen Kim
The diagnosis of solid pseudopapillary neoplasms (SPNs) is challenging because some SPNs share many similar morphological and immunohistochemical features with other pancreatic neoplasms. In this study, we investigated potential diagnostic markers of SPN. Based on the SPN-specific upregulated genes from a previous DNA microarray and proteome study, we selected six immunohistochemical markers [beta-catenin, androgen receptor (AR), lymphoid enhancer-binding factor 1 (LEF1), transcription factor for immunoglobulin heavy-chain enhancer 3 (TFE3), fused in sarcoma (FUS), and WNT inhibitory factor 1 (WIF-1)]...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29211317/neurobiology-of-gender-identity-and-sexual-orientation
#8
REVIEW
Charles E Roselli
Sexual identity and sexual orientation are independent components of a person's sexual identity. These dimensions are most often in harmony with each other and with an individual's genital sex, but not always. This review discusses the relationship of sexual identity and sexual orientation to prenatal factors that act to shape the development of the brain and the expression of sexual behaviors in animals and humans. One major influence discussed relates to organizational effects that the early hormone environment exerts on both gender identity and sexual orientation...
December 6, 2017: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/29210800/molecular-modifiers-of-hormone-receptor-action-decreased-androgen-receptor-expression-in-mismatch-repair-deficient-endometrial-endometrioid-adenocarcinoma
#9
Qiong Gan, Suzanne Crumley, Russell R Broaddus
Endometrial endometrioid carcinoma is related to estrogen excess and expression of estrogen and progesterone receptors. Epidemiological evidence suggests that exposure to elevated androgens, as in polycystic ovarian syndrome, increases the risk of endometrial cancer. Factors impacting androgen receptor (AR) expression are not well studied. Mismatch repair (MMR) deficiency due to MLH1 gene methylation is one of the most common molecular alterations in endometrial cancer, occurring in 15% to 20% of cases. MLH1 methylation can be associated with decreased expression of other genes, so we examined the effect of MMR status on AR expression...
November 28, 2017: International Journal of Gynecological Pathology
https://www.readbyqxmd.com/read/29209278/follicle-stimulating-hormone-regulates-igfbp-gene-expression-directly-or-via-downstream-effectors-to-modulate-igf3-effects-on-zebrafish-spermatogenesis
#10
Diego Safian, Henk J G van der Kant, Diego Crespo, Jan Bogerd, Rüdiger W Schulz
Previous work showed that pharmacological inactivation of Igf-binding proteins (Igfbps), modulators of Igf activity, resulted in an excessive differentiation of type A undifferentiated (Aund) spermatogonia in zebrafish testis in tissue culture when Fsh was present in the incubation medium. Using this testis tissue culture system, we studied here the regulation of igfbp transcript levels by Fsh and two of its downstream effectors, Igf3 and 11-ketotestosterone (11-KT). We also explored how Fsh-modulated igfbp expression affected spermatogonial proliferation by adding or removing the Igfbp inhibitor NBI-31772 at different times...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29209210/critical-role-of-hepatic-cyp450s-in-the-testis-specific-toxicity-of-5r-5-hydroxytriptolide-in-c57bl-6-mice
#11
Cunzhi Yu, Yu Li, Mingxia Liu, Man Gao, Chenggang Li, Hong Yan, Chunzhu Li, Lihan Sun, Liying Mo, Chunyong Wu, Xinming Qi, Jin Ren
Low solubility, tissue accumulation, and toxicity are chief obstacles to developing triptolide derivatives, so a better understanding of the pharmacokinetics and toxicity of triptolide derivatives will help with these limitations. To address this, we studied pharmacokinetics and toxicity of (5R)-5-hydroxytriptolide (LLDT-8), a novel triptolide derivative immunosuppressant in a conditional knockout (KO) mouse model with liver-specific deletion of CYP450 reductase. Compared to wild type (WT) mice, after LLDT-8 treatment, KO mice suffered severe testicular toxicity (decreased testicular weight, spermatocytes apoptosis) unlike WT mice...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29207642/crosstalk-in-competing-endogenous-rna-network-reveals-the-complex-molecular-mechanism-underlying-lung-cancer
#12
Xiang Jin, Yinghui Guan, Hui Sheng, Yang Liu
We investigated the transcriptional mechanism underlying lung cancer development. RNA sequencing analysis was performed on blood samples from lung cancer cases and healthy controls. Differentially expressed microRNAs (miRNAs), circular RNAs (circRNAs), mRNAs (genes), and long non-coding RNAs (lncRNA) were identified, followed by pathway enrichment analysis. Based on miRNA target interactions, a competing endogenous network was established and significant nodes were screened. Differentially expressed transcriptional factors were retrieved from the TRRUST database and the transcriptional factor regulatory network was constructed...
October 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/29196557/selexglm-differentiates-androgen-and-glucocorticoid-receptor-dna-binding-preference-over-an-extended-binding-site
#13
Liyang Zhang, Gabriella D Martini, H Tomas Rube, Judith F Kribelbauer, Chaitanya Rastogi, Vincent D FitzPatrick, Jon C Houtman, Harmen J Bussemaker, Miles A Pufall
The DNA-binding interfaces of the androgen (AR) and glucocorticoid (GR) receptors are virtually identical, yet these transcription factors share only about a third of their genomic binding sites and regulate similarly distinct sets of target genes. To address this paradox, we determined the intrinsic specificities of the AR and GR DNA binding domains using a refined version of SELEX-seq. We developed an algorithm, SelexGLM, that quantifies binding specificity over a large (31 bp) binding-site by iteratively fitting a feature-based generalized linear model to SELEX probe counts...
December 1, 2017: Genome Research
https://www.readbyqxmd.com/read/29194690/a-carbon-21-steroidal-metabolite-from-progestin-20%C3%AE-hydroxy-5%C3%AE-dihydroprogesterone-stimulates-the-androgen-receptor-in-prostate-cancer-cells
#14
Takashi Ando, Tsutomu Nishiyama, Itsuhiro Takizawa, Yoshimichi Miyashiro, Noboru Hara, Yoshihiko Tomita
BACKGROUND: Clarifying the mechanisms underlying prostate cancer (PC) progression and resistance to androgen deprivation therapy (ADT) is an urgent clinical issue. ADT influences steroidal metabolism in patients with PC and promotes the accumulation of carbon 21 steroids (C21s), such as progestin. Because the enzymes responsible for C21s metabolism are similar to those for androgen metabolism, PC cells may be able to metabolize C21s intracellularly. Therefore, there is a possibility that intracrine C21s are implicated in PC progression and resistance to ADT, and the influence of C21s on PC cells is yet to be elucidated...
December 1, 2017: Prostate
https://www.readbyqxmd.com/read/29181434/androgen-receptor-ar-cistrome-in-prostate-differentiation-and-cancer-progression
#15
Fengtian Wang, Hari K Koul
Despite the progress in development of better AR-targeted therapies for prostate cancer (PCa), there is no curative therapy for castration-resistant prostate cancer (CRPC). Therapeutic resistance in PCa can be characterized in two broad categories of AR therapy resistance: the first and most prevalent one involves restoration of AR activity despite AR targeted therapy, and the second one involves tumor progression despite blockade of AR activity. As such AR remains the most attractive drug target for CRPC. Despite its oncogenic role, AR signaling also contributes to the maturation and differentiation of prostate luminal cells during development...
2017: American Journal of Clinical and Experimental Urology
https://www.readbyqxmd.com/read/29170528/kidney-androgen-regulated-protein-kap-transgenic-mice-are-protected-against-high-fat-diet-induced-metabolic-syndrome
#16
Beatriz Bardaji de Quixano, Josep A Villena, Miguel Aranda, Gemma Brils, Antoni Cuevas, Théana Hespel, Haizea Lekuona, Cristina Súarez, Olga Tornavaca, Anna Meseguer
Metabolic Syndrome (MS) is reaching epidemic proportions with significant social and economical burden worldwide. Since the molecular basis of MS remains poorly defined, we investigated the impact of KAP, a kidney specific androgen-regulated gene, in the development of high fat-diet (hfd)-induced MS. Tg mice overexpressing KAP specifically in proximal tubule cells of the kidney exhibited reduced body weight and lower liver and adipose tissue weight compared to control littermates when fed a hfd. KAP Tg mice showed diminished adipocyte hypertrophy and reduced hepatic steatosis, significantly correlating with expression of relevant molecular markers and lower lipid content in liver...
November 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29162470/incorporation-of-metabolic-enzymes-to-improve-predictivity-of-reporter-gene-assay-results-for-estrogenic-and-anti-androgenic-activity
#17
Barbara M A van Vugt-Lussenburg, Rosan B van der Lee, Hai-Yen Man, Irene Middelhof, Abraham Brouwer, Harrie Besselink, Bart van der Burg
Identification and monitoring of so-called endocrine-disrupting compounds has received ample attention; both the OECD and the United States Environmental Protection Agency (US EPA) have designed tiered testing approaches, involving in vitro bioassays to prioritize and partly replace traditional animal experiments. Since the estrogen (ER) and androgen (AR) receptor are frequent targets of endocrine disrupting chemicals, bioassays detecting interaction with these receptors have a high potential to be of use in risk assessment of endocrine active compounds...
November 21, 2017: Reproductive Toxicology
https://www.readbyqxmd.com/read/29156689/implications-of-pi3k-akt-inhibition-on-rest-protein-stability-and-neuroendocrine-phenotype-acquisition-in-prostate-cancer-cells
#18
Ruiqui Chen, Yinan Li, Ralph Buttyan, Xuesen Dong
Treatment-induced neuroendocrine prostate cancer (t-NEPC) is an aggressive subtype of prostate cancer (PCa) that arises as a consequence of rigorous androgen receptor (AR) pathway inhibition (ARPI) therapies. While the PI3K/AKT pathway has been investigated as a co-therapeutic target with ARPI for advanced PCa, whether this strategy can prevent tumor progression to t-NEPC remains unknown. Here, we report that PI3K/AKT inhibition alone reduces RE-1 silencing transcription factor (REST) protein expression and induces multiple NE markers in PCa cells...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29153843/aberrant-activation-of-a-gastrointestinal-transcriptional-circuit-in-prostate-cancer-mediates-castration-resistance
#19
Shipra Shukla, Joanna Cyrta, Devan A Murphy, Edward G Walczak, Leili Ran, Praveen Agrawal, Yuanyuan Xie, Yuedan Chen, Shangqian Wang, Yu Zhan, Dan Li, Elissa W P Wong, Andrea Sboner, Himisha Beltran, Juan Miguel Mosquera, Jessica Sher, Zhen Cao, John Wongvipat, Richard P Koche, Anuradha Gopalan, Deyou Zheng, Mark A Rubin, Howard I Scher, Ping Chi, Yu Chen
Prostate cancer exhibits a lineage-specific dependence on androgen signaling. Castration resistance involves reactivation of androgen signaling or activation of alternative lineage programs to bypass androgen requirement. We describe an aberrant gastrointestinal-lineage transcriptome expressed in ∼5% of primary prostate cancer that is characterized by abbreviated response to androgen-deprivation therapy and in ∼30% of castration-resistant prostate cancer. This program is governed by a transcriptional circuit consisting of HNF4G and HNF1A...
November 3, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29147905/transcriptional-regulation-of-dj-1
#20
Kazuko Takahashi-Niki, Takeshi Niki, Sanae M M Iguchi-Ariga, Hiroyoshi Ariga
DJ-1 is an oncogene and also a causative gene for familial Parkinson's disease. DJ-1 has various functions, and the oxidative status of a cysteine residue at position 106 (C106) is crucial for determination of the activation level of DJ-1.DJ-1 binds to many proteins, including various transcription factors, and acts as a coactivator or corepressor for regulating their target genes without direct binding to DNA, thereby affecting various cell functions. DJ-1-regulating transcription factors and their modified proteins are the androgen receptor and its regulatory proteins, p53; polypyrimidine tract-binding protein-associated splicing factor (PSF); Keap1, an inhibitor for nuclear factor erythroid2-related factor 2 (Nrf2); sterol regulatory element-binding protein (SREBP); Ras-responsive element-binding protein (RREB1); signal transducer and activator of transcription 1 (STAT1); and Nurr1...
2017: Advances in Experimental Medicine and Biology
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