Searchable abstracts of presentations at key conferences in endocrinology
Previous issue | Volume 54 | NuclearReceptors2018 | Next issue

Nuclear Receptors: New Roles for Nuclear Receptors in Development, Health and Disease Conference 2018

ea0054p1 | (1) | NuclearReceptors2018

Single-molecule analysis of peroxisome proliferator-activated receptor γ2 and α reveal subtype specific differences in chromatin binding dynamics

Jensen Rikke AM , Paakinaho Ville , Presman Diego M , Swinstead Erin E , Schiltz R Louis , Ball David A , Karpova Tatiana S , Mandrup Susanne , Hager Gordon L

The peroxisome proliferator-activated receptors (PPARs) display a high degree of conservation in the DNA- and ligand-binding domains. Despite these sequence similarities, the PPARs show distinct functions, even when co-expressed. Many experimental approaches have been employed to determine the molecular mechanisms that underlie their subtype-specific characteristics. However, these approaches have largely relied on cell population based studies, such as ChIP-seq. Here we have ...

ea0054p2 | (1) | NuclearReceptors2018

Next generation glucocorticoid receptor modulators

Edman Karl , Belfield Graham , Dearman Matthew , Edenro Goran , Geschwindner Stefan , Hegelund-Myrback Tove , Hemmerling Martin , Hendrickx Ramon , Keen Christina , Karrman-Mardh Carina , Lepisto Matti , Mitra Suman , Monkley Susan , Prothon Susanne , Ripa Lena , Steele John , Vaarala Outi , Wissler Lisa , Oberg Lisa

Synthetic glucocorticoids bind to the glucocorticoid receptor (GR) and have been used for nearly 70 years to treat inflammatory diseases. However, their use is limited by adverse effects such as diabetes, muscle wasting and osteoporosis. High throughput screening identified a novel non-steroidal scaffold with great potential for chemical optimization. Through rational design we developed the indazole ether series which combines high potency with structural motifs that provide ...

ea0054p3 | (1) | NuclearReceptors2018

Interactions between AR coregulators, TRIM24 and TRIM28, in Castrate Resistant Prostate Cancer (CRPC)

Leach Damien A , Bevan Charlotte L

Castrate Resistant Prostate Cancer (CRPC) is the inevitable outcome of hormone treatment for advanced disease. Although no longer dependent on high levels of androgens, the androgen receptor (AR) remains active and there is evidence that other nuclear receptors (NRs) can drive CRPC progression and/or therapy resistance. NRs share a repertoire of essential coregulators: proteins possessing the ability to aid or repress NR action and have been proposed as a potential mechanism f...

ea0054p4 | (1) | NuclearReceptors2018

Selective disruption of ERα expression in dendritic cells of lupus prone mice results in female-specific reduced survival

Cunningham Melissa A , Wirth Jena R , Eudaly Jackie , Gilkeson Gary S

Systemic lupus erythematosus (SLE) is a disease that disproportionately affects females. We previously showed that a functional knockout of estrogen receptor alpha (ERαKO) resulted in significantly reduced renal disease and increased survival in murine lupus. The mechanism of this effect, which requires estrogen, is not known. Interestingly, an ERα−/− (null mutant) mouse is not similarly protected. We and others have demonstrated a role for ERα in de...

ea0054p5 | (1) | NuclearReceptors2018

Glucocorticoid receptor inhibits ER-mediated pro-proliferative gene expression

Tonsing-Carter E , Kim CR , Hernandez KM , Bowie KR , West DC , Chandarlapaty S , Greene GL , Conzen SD

Early-stage ER+ breast cancer (BC) with high tumor glucocorticoid receptor (GR) expression is associated with improved long term relapse-free survival compared to tumors with low GR expression. In addition, GR activity inhibits ER-mediated BC cell proliferation. We therefore hypothesized that GR and ER engage in nuclear receptor crosstalk to influence pro-proliferative gene expression, thus contributing to a better outcome in ER+/GR+ breast cancer. To understand the mechanisms...

ea0054p6 | (1) | NuclearReceptors2018

The impact of 27-hydroxycholesterol on endometrial cancer proliferation

Saunders Philippa TK , Collins Frances , Cousins Fiona , Esnal-Zufiaurre1 Arantza , Gibson Douglas A

Endometrial cancer (EC) is the most common gynaecological malignancy. Obesity is a major risk factor for EC and is associated with elevated cholesterol. 27-Hydroxycholesterol (27HC) is a cholesterol metabolite that functions as an endogenous agonist for Liver X Receptor (LXR) and a selective estrogen receptor modulator (SERM). Exposure to estrogenic ligands increases risk of developing EC however the impact of 27HC on EC is unknown.Samples of stage 1 EC ...

ea0054p7 | (1) | NuclearReceptors2018

MIR-96 regulates retinoic acid receptor gamma cross-talk with the androgen receptor to drive aggressive prostate cancer

Long Mark D , Rosario Spencer , Sucheston-Campbell Lara E , Smiraglia Dominic J , Campbell Moray J

The retinoic acid receptor gamma (RARg, encoded by NR1B3/RARG) is significantly downregulated but not mutated in the MSKCC and PRAD prostate cancer (PCa) cohorts in the Cancer Genome Atlas (TCGA) data. We investigated the consequences of modifying RARg expression.Independent of ligand, stable RARg knockdown stimulated RWPE-1 and LNCaP cells proliferation, changed the cell cycle profile and significantly altered global gene expression patterns th...