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

ea0054is1 | (1) | NuclearReceptors2018

MicroRNA regulation of androgen signalling

Fletcher Claire E , Sita-Lumsden Ailsa , Dart Alwyn , Shibakawa Akifumi , Sulpice Eric , Combe Stephanie , Leach Damien A , de Bono Johann , Lupold SE , McGuire SE , Gidrol Xavier , Bevan Charlotte L

Androgens initially drive prostate tumour growth. Although in advanced disease there is no longer dependence on circulating androgens, the androgen receptor (AR) remains a key driver of this lethal stage thus new ways to inhibit its activity are required. MicroRNAs play vital roles in prostate cancer (PCa) development, progression and metastasis. Previous studies have examined microRNAs dysregulated in PCa, and also identified androgen-regulated microRNAs. We approached microR...

ea0054is2 | (1) | NuclearReceptors2018

Androgen and estrogen receptors in breast tissues: opponents or teammates?

Hickey Theresa E

The balance of androgen and estrogen hormone activity determines the degree of breast development in males and females. A predominance of androgen action impedes whereas a predominance of estrogen action promotes breast development. This sex hormone antagonism is mechanistically mediated by androgen and estrogen receptors (AR, ER). The alpha form of ER (ERα) is required for normal breast development and is the driving oncogene in the majority of breast cancers. The AR is ...

ea0054is3 | (1) | NuclearReceptors2018

Nuclear receptors, transcriptional enhancers, and gene regulation

Franco Hector L , Murakami Shino , Hou Tim Y , Vasquez Yasmin M , Liu Ziying , Nagari Anusha , Malladi Venkat S , Nandu Tulip , Kraus W Lee

Transcriptional enhancers, which function as nucleation sites for the assembly of transcription-regulating complexes across the genome, drive cell type-specific patterns of gene expression that underlie the distinct biological properties of different cell types. Although many features of active enhancers (e.g., H3K4me1, H3K27ac, enrichment of p300/CBP and Mediator, and enhancer RNA production) have been defined by genomic assays, the roles of these features in ERα enhance...

ea0054is4 | (1) | NuclearReceptors2018

Estrogen receptor cistromics in breast tumors: from biomarkers to novel drug targets

Flach Koen Dorus , Periyasamy Manikandan , Jadhav Ajit , Hickey Theresa E , Opdam Mark , Patel Hetal , Canisius Sander , Wilson David M , Dorjsuren Dorjbal , Nieuwland Marja , Kluin Roel , Zakharov Alexey V , Wesseling Jelle , Wessels Lodewyk Frederik Ary , Linn Sabine Charlotte , Tilley Wayne D , Simeonov Anton , Ali Simak , Zwart Wilbert

Estrogen receptor α (ERα) is a key transcriptional regulator in the majority of breast cancers. ERα-positive patients are frequently treated with tamoxifen, but resistance is common. Through ChIP-seq analyses, we presviously identified direct target genes of ERα acting in complex with SRC1, SRC2 or SRC3 (Zwart et al., 2011 EMBO J). Only the 111 genes there were under direct control of ERα in conjunction with SRC3 (but not the other two p160s) predicted...

ea0054is5 | (1) | NuclearReceptors2018

Rapid, cytoplasmic actions of the glucocorticoid receptor impact on cell movement

Kershaw Stephen , Morgan David J , Brass Andrew , Boyd James , Spiller David , Zindy Egor , Iqbal Mudassar , Matthews Laura C , Ray David W

Glucocorticoids (GCs) act through the glucocorticoid receptor (GR) to regulate immunity, energy metabolism, and tissue repair. The inactive GR is held in the cytoplasm in a multi-protein complex, which upon ligand binding undergoes a conformational change. Activated GR translocates to the nucleus to regulate gene expression (over hours), but some effects occur more rapidly. GCs inhibit cell migration through an uncertain mechanism. We now show a very rapid effect, and surprisi...

ea0054is6 | (1) | NuclearReceptors2018

Androgens and endometrial function: replication, repair and regeneration

Gibson Douglas A , Simitsidellis Ioannis , Collins Frances , Esnal-Zufiaurre Arantza , Saunders Philippa TK

The human endometrium is a complex multicellular tissue the prime function of which is to provide a receptive environment during a fertile cycle. The tissue responds to steroid hormones exhibiting dynamic cyclical regeneration, angiogenesis, differentiation (decidualisation) and inflammation. In the absence of an embryo the inner surface is shed and repaired without scarring (menstruation). The endometrium exhitbits spatial and temporal expression of androgen receptors (AR) in...

ea0054is7 | (1) | NuclearReceptors2018

Clinically-relevant contexts for AR variants in prostate cancer

Dehm Scott M

The androgen receptor (AR) functions as a master transcriptional regulator of prostate tissue homeostasis. This master transcriptional regulator function is maintained in prostate cancer. Therefore, prostate cancer is an androgen-dependent disease and suppression of AR transcriptional activity with androgen deprivation therapy (ADT) is an effective systemic therapy. However, development of therapy resistance and transition to castration resistant prostate cancer (CRPC) represe...

ea0054is8 | (1) | NuclearReceptors2018

Direct and indirect effects of androgens on the musculoskeletal system

Claessens Frank , Michael Laurent , Dubois Vanessa , Khalil Rougin , Jardi Ferran , Vanderschueren Dirk

Global knockout models of the androgen receptor (ARKO) illustrates the many roles androgens and their receptor have in the development of male reproductive organs and the gender differences in many features like the musculoskeletal system. However, neither the global ARKO nor orchidectomy models discriminate between direct and indirect effects of androgens. To determine direct and indirect effects of androgens on muscle, we developed a muscle-specific ARKO (called satARKO for ...

ea0054is9 | (1) | NuclearReceptors2018

Progesterone receptor regulation of breast cancer cell translation

Finlay-Schultz Jessica , Gillen Austin E , Brechbuhl Heather M , Matthews Shawna B , Jacobsen Britta M , Bentley David L , Kabos Peter , Sartorius Carol A

Progesterone receptors (PR) are long recognized to suppress estrogen receptor (ER) mediated transcription in breast cancers. However, a mechanistic basis for this repression has been lacking. Recent reports indicate this occurs, in part, through global repositioning of ER on chromatin in the presence of selective PR modulators (SPRMS), both agonists and antagonists [1, 2]. The goal of our studies was to further understand the mechanisms by which PR impacts estrogen-dependent g...

ea0054is10 | (1) | NuclearReceptors2018

Modulating glucocorticoid receptor function in breast and prostate cancer

Tonsing-Carter E. , Long T. , West D.C. , Harkless R. , Dolcen D.N. , Hosfield D. , Greene G.L. , Szmulewitz R.Z. , Conzen S.D.

In normal physiology, glucocorticoid receptor (GR) activation regulates cell type-dependent genes whose products influence metabolism, inflammation, cell cycle and apoptosis/cell survival pathways. Synthetic GR agonists, or glucocorticoids (GCs), are often used to treat hematologic malignancies because of GR’s ability to induce proapoptotic gene expression, inhibit nuclear factor–κB, and induce cell cycle arrest. In contrast, recent examination of GR expression ...

ea0054is11 | (1) | NuclearReceptors2018

Protein factors involved in 3D genome organization & transcription regulation

Ruan Yijun

The human genome is over 2 meters in length, which has to be folded in micrometer-sized nuclear space for proper functions. Although most of our understandings in the human genome are based on linear explanations, it has been speculated that the three-dimensional (3D) and high-order organization of the genome must play important roles in framing the mechanisms of nuclear process such as transcription regulation. Recent advance in 3D genome mapping technologies and sophisticate...

ea0054is12 | (1) | NuclearReceptors2018

Nuclear receptor networks in male fertility

Martinot Emmanuelle , Sedes Lauriane , Baptissart Marine , Holota Helene , Angelique De Haze , Beaudoin Claude , Volle David H

Male fertility is controlled by complex interactions between hypothalamus, pituitary, and testis. The major functions of the testis include production of spermatozoa and synthesis of hormones. Testosterone is produced by the testicular Leydig cells and ensures male fertility. Testosterone is involved in the development of gonad, the attainment of puberty, the maintenance of secondary sexual characteristics as well as in spermatogenesis process. Many studies have highlighted th...

ea0054is13 | (1) | NuclearReceptors2018

Enhancers mapping uncovers phenotypic heterogeneity and evolution in patients with luminal breast cancer

Patten Darren K , Corleone Giacomo , Győrffy Balazs , Erdős Edina , Saiakhova Alina , Goddard Kate , Vingiani Andrea , Shousha Sami , Pongor Lőrinc Sandor , Hadjiminas Dimitri J , Schiavon Gaia , Barry Peter , Palmieri Carlo , Coombes Raul C , Scacheri Peter , Pruneri Giancarlo , Magnani Luca

The degree of intrinsic and interpatient phenotypic heterogeneity and its role in tumour evolution is poorly understood. Phenotypic divergence can be achieved via the inheritance of alternative transcriptional programs. Cell-type specific transcription is maintained through the activation of epigenetically-defined regulatory regions including promoters and enhancers. In this work, we annotated the epigenome of 47 primary and metastatic oestrogen-receptor (ERα)-positive br...

ea0054is14 | (1) | NuclearReceptors2018

The structural basis of chromatin reprogramming by steroid receptors

Hager GL , Paakinaho V , Johnson TA , Chereji RV , Clark DJ , Swinstead EE , Presman DM

Localized transitions in chromatin structure accompany nuclear receptor binding events in mammalian cells. These remodeling processes are critical to determine the binding landscape for steroid receptors (SRs) in cancer cells. Multiple reports indicate that steroid receptors (ER, GR, AR, PR) can regulate the binding patterns for each other, particularly during cancer progression. Elucidation of the mechanisms by which these ‘chromatin opening’ processes occur is cent...