A Godoy

A Haelens

A Monge

AN Vis

AO Brinkmann

B Cinar

B Gottlieb

B He

B Tiwary

BA Evans

C Cai

CA Berrevoets

CA Heinlein

Colin W. Hay

CT Kesler

CT Wu

D Ricketson

DJ Lamb

EB Askew

EP Gelmann

ER Hyytinen

G Buchanan

G Chen

G Verrijdt

GN Brooke

GP Reddy

H Faus

H Takahashi

HI Scher

HJ Dubbink

HT Bruggenwirth

I Ahrens-Fath

Iain J. McEwan

IJ McEwan

J Brodie

J Duff

J Edwards

J Geller

J Reid

J Tan

J Veldscholte

JA Locke

JD Wilson

Jean-Marc A. Lobaccaro

K Evaul

K Haapala

KB Cleutjens

KE Knudsen

KH Chang

KK Waltering

KM Lakshman

LJ Blok

M Fu

M Jagla

M Marcelli

M Sun

M Uemura

M Welsh

ME Baker

ME Taplin

MJ Linja

MM Centenera

MM Shen

N Mononen

OA O'Mahony

PA Watson

PE de Ruiter

Q Wang

R Betney

R Chenna

R Hu

R Schule

RJ Andersen

S Baron

S Haile

S Koochekpour

SM Dehm

SM Powell

SS Dutt

SS Taneja

ST Page

TH Li

TM Tanner

W Li

Y Chen

Y Gluzman

Y Niu

Y Ogino

YD Li

Z Guo

PLoS ONE

English

PubMed

Hay, Colin W

McEwan, Iain J

Aberdeen University Research

3betahydroxysteroid dehydrogenase is a possible pharmacological target in the treatment of castration-resistant prostate cancer.

5alpha-reductase type 3 expression in human benign and malignant tissues: A comparative analysis during prostate cancer progression.

A 629RKLKK633 motif in the hinge region controls the androgen receptor at multiple levels.

A conformational switch in the ligand-binding domain regulates the dependence of the glucocorticoid receptor on Hsp90.

A novel androgen receptor splice variant is up-regulated during prostate cancer progression and promotes androgen depletion-resistant growth.

A promoting role of androgen receptor in androgen-sensitive and -insensitive prostate cancer cells.

A splicing variant of the androgen receptor detected in a metastatic prostate cancer exhibits exclusively cytoplasmic actions.

Acetylation of androgen receptor enhances coactivator binding and promotes prostate cancer cell growth.

Activation of phosphatidylinositol 3-kinase/Akt pathway by androgen through interaction of p85alpha, androgen receptor, and src.

Amplification and overexpression of androgen receptor gene in hormonerefractory prostate cancer.

An androgen receptor NH2-terminal conserved motif interacts with the COOH terminus of the Hsp70-interacting protein (CHIP).

An androgen response element in a far upstream enhancer region is essential for high, androgen-regulated activity of the prostate-specific antigen promoter.

An S296R mutation in the human androgen receptor causes activation of the receptor by non-androgenic steroids and stronger inhibition by the nuclear receptor corepressor N-coR.

Androgen levels increase by intratumoral de novo steroidogenesis during progression of castration-resistant prostate cancer.

Androgen receptor acetylation sites differentially regulate gene control.

Androgen receptor alterations in prostate cancer relapsed during a combined androgen blockade by orchiectomy and bicalutamide.

Androgen receptor function is modulated by the tissue-specific AR45 variant.

Androgen receptor gene amplification and protein expression in hormone refractory prostate cancer.

Androgen receptor in prostate cancer.

Androgen receptor is a tumor suppressor and proliferator in prostate cancer.

Androgen receptor mediates non-genomic activation of phosphatidylinositol 3-OH kinase in androgen-sensitive epithelial cells.

Androgen receptor mutants detected in recurrent prostate cancer exhibit diverse functional characteristics.

Androgen receptor mutations identified in prostate cancer and androgen insensitivity syndrome display aberrant ART-27 coactivator function.

Androgen receptor mutations in prostate cancer.

Androgen receptor regulates a distinct transcription program in androgen-independent prostate cancer.

Androgen receptor signaling and mutations in prostate cancer.

Androgen receptor structural and functional elements: Role and regulation in prostate cancer.

ART-27, an androgen receptor coactivator regulated in prostate development and cancer.

Biology of progressive, castration-resistant prostate cancer: Directed therapies targeting the androgen-receptor signaling axis.

Cancer fact sheet,

Cancer facts and figures

Change of specificity mutations in androgen-selective enhancers. evidence for a role of differential DNA binding by the androgen receptor.

Clinical review 134: The endocrinology of prostate cancer.

Constitutively active androgen receptor splice variants expressed in castrationresistant prostate cancer require full-length androgen receptor.

Dehydroepiandrosterone activates mutant androgen receptors expressed in the androgen-dependent human prostate cancer xenograft CWR22 and LNCaP cells.

Dependence of selective gene activation on the androgen receptor NH2- and COOH-terminal interaction.

Dihydrotestosterone synthesis bypasses testosterone to drive castration-resistant prostate cancer.

Distinct recognition modes of FXXLF and LXXLL motifs by the androgen receptor.

Evolutionary history and functional characterization of androgen receptor genes in jawed vertebrates.

Functional interactions of the AF-2 activation domain core region of the human androgen receptor with the amino-terminal domain and with the transcriptional coactivator TIF2 (transcriptional intermediary factor2).

Increased expression of androgen receptor sensitizes prostate cancer cells to low levels of androgens.

Increased prostate cell proliferation and loss of cell differentiation in mice lacking prostate epithelial androgen receptor.

Intra-domain communication between the Nterminal and DNA-binding domains of the androgen receptor: Modulation of androgen response element DNA binding.

Intratumoral de novo steroid synthesis activates androgen receptor in castration-resistant prostate cancer and is upregulated by treatment with CYP17A1 inhibitors.

Key targets of hormonal treatment of prostate cancer. part 2: The androgen receptor and 5alpha-reductase.

Ligandindependent androgen receptor variants derived from splicing of cryptic exons signify hormone-refractory prostate cancer.

Low incidence of androgen receptor gene mutations in human prostatic tumors using single strand conformation polymorphism analysis.

Many transcription factors interact synergistically with steroid receptors.

Mechanisms of androgen receptor activation in advanced prostate cancer: Differential co-activator recruitment and gene expression.

Mechanisms of androgen receptor signalling via steroid receptor coactivator-1 in prostate.

Modulation of androgen receptor activation function 2 by testosterone and dihydrotestosterone.

Molecular analysis of the androgen receptor in ten prostate cancer specimens obtained before and after androgen ablation.

Molecular biology of the androgen receptor.

Molecular genetics of prostate cancer: New prospects for old challenges.

Molecular mechanisms of androgen receptor-mediated gene regulation: Structure-function analysis of the AF-1 domain.

Molecular mechanisms of castration-resistant prostate cancer progression.

Multiple sequence alignment with the clustal series of programs.

Mutation of histidine 874 in the androgen receptor ligand-binding domain leads to promiscuous ligand activation and altered p160 coactivator interactions. Mol Endocrinol

Mutation of the androgen-receptor gene in metastatic androgen-independent prostate cancer.

Mutations at the boundary of the hinge and ligand binding domain of the androgen receptor confer increased transactivation function.

Novel 5 alpha-steroid reductase (SRD5A3, type-3) is overexpressed in hormonerefractory prostate cancer.

Parallel evolution between aromatase and androgen receptor in the animal kingdom.

Pattern of somatic androgen receptor gene mutations in patients with hormonerefractory prostate cancer.

Penning TM (2010) Partners in crime: Deregulation of AR activity and androgen synthesis in prostate cancer.

Persistent intraprostatic androgen concentrations after medical castration in healthy men.

Phosphoinositide 3-kinase-independent non-genomic signals transit from the androgen receptor to Akt1 in membrane raft microdomains.

Prevalence of androgen receptor gene mutations in latent prostatic carcinomas from japanese men.

Profiling human androgen receptor mutations reveals treatment effects in a mouse model of prostate cancer.

Rationale for blockade of adrenal as well as testicular androgens in the treatment of advanced prostate cancer.

Regression of castrate-recurrent prostate cancer by a small-molecule inhibitor of the aminoterminus domain of the androgen receptor.

Regulatory processes affecting androgen receptor expression, stability, and function: Potential targets to treat hormone-refractory prostate cancer.

Role of conserved hydrophobic amino acids in androgen receptor AF-1 function.

Role of dihydrotestosterone in androgen action.

Selection for androgen receptor mutations in prostate cancers treated with androgen antagonist.

Smooth muscle cell-specific knockout of androgen receptor: A new model for prostatic disease.

Splicing of a novel androgen receptor exon generates a constitutively active androgen receptor that mediates prostate cancer therapy resistance.

Steroid receptor phylogeny and vertebrate origins.

Structural basis for androgen receptor interdomain and coactivator interactions suggests a transition in nuclear receptor activation function dominance.

Subcellular localization modulates activation function 1 domain phosphorylation in the androgen receptor.

Substitution of Ala564 in the first zinc cluster of the deoxyribonucleic acid (DNA)-binding domain of the androgen receptor by asp, asn, or leu exerts differential effects on DNA binding.

SV40-transformed simian cells support the replication of early SV40 mutants.

Synergism between androgens and protein kinase-C on androgen-regulated gene expression.

Targeting the androgen receptor pathway in prostate cancer.

Targeting the stromal androgen receptor in primary prostate tumors at earlier stages.

The androgen receptor gene mutations database (ARDB):

The androgen receptor in LNCaP cells contains a mutation in the ligand binding domain which affects steroid binding characteristics and response to antiandrogens.

The androgen receptor interacts with multiple regions of the large subunit of general transcription factor TFIIF.

The contribution of different androgen receptor domains to receptor dimerization and signaling.

The effects of injected testosterone dose and age on the conversion of testosterone to estradiol and dihydrotestosterone in young and older men.

The hinge region regulates DNA binding, nuclear translocation, and transactivation of the androgen receptor.

The human androgen receptor: Domain structure, genomic organization and regulation of expression.

Transcriptional regulation of androgen receptor gene expression in sertoli cells and other cell types.

Two percent of finnish prostate cancer patients have a germ-line mutation in the hormone-binding domain of the androgen receptor gene.

Unfaithfulness and promiscuity of a mutant androgen receptor in a hormonerefractory prostate cancer.

The impact of point mutations in the human androgen receptor : classification of mutations on the basis of transcriptional activity

<div><p>Androgen receptor mediated signaling drives prostate cancer cell growth and survival. Mutations within the receptor occur infrequently in prostate cancer prior to hormonal therapy but become prevalent in incurable androgen independent and metastatic tumors. Despite the determining role played by the androgen receptor in all stages of prostate cancer progression, there is a conspicuous dearth of comparable data on the consequences of mutations. In order to remedy this omission, we have combined an expansive study of forty five mutations which are predominantly associated with high Gleason scores and metastatic tumors, and span the entire length of the receptor, with a literature review of the mutations under investigation. We report the discovery of a novel prevalent class of androgen receptor mutation that possesses loss of function at low levels of androgen yet transforms to a gain of function at physiological levels. Importantly, mutations introducing constitutive gain of function are uncommon, with the majority of mutations leading to either loss of function or no significant change from wild-type activity. Therefore, the widely accepted supposition that androgen receptor mutations in prostate cancer result in gain of function is appealing, but mistaken. In addition, the transcriptional outcome of some mutations is dependent upon the androgen receptor responsive element. We discuss the consequences of these findings and the role of androgen receptor mutations for prostate cancer progression and current treatment options.</p> </div

Colin W. Hay (179733)

Iain J. McEwan (179736)

The Francis Crick Institute

The Impact of Point Mutations in the Human Androgen Receptor: Classification of Mutations on the Basis of Transcriptional Activity

Androgen receptor mediated signaling drives prostate cancer cell growth and survival. Mutations within the receptor occur infrequently in prostate cancer prior to hormonal therapy but become prevalent in incurable androgen independent and metastatic tumors. Despite the determining role played by the androgen receptor in all stages of prostate cancer progression, there is a conspicuous dearth of comparable data on the consequences of mutations. In order to remedy this omission, we have combined an expansive study of forty five mutations which are predominantly associated with high Gleason scores and metastatic tumors, and span the entire length of the receptor, with a literature review of the mutations under investigation. We report the discovery of a novel prevalent class of androgen receptor mutation that possesses loss of function at low levels of androgen yet transforms to a gain of function at physiological levels. Importantly, mutations introducing constitutive gain of function are uncommon, with the majority of mutations leading to either loss of function or no significant change from wild-type activity. Therefore, the widely accepted supposition that androgen receptor mutations in prostate cancer result in gain of function is appealing, but mistaken. In addition, the transcriptional outcome of some mutations is dependent upon the androgen receptor responsive element. We discuss the consequences of these findings and the role of androgen receptor mutations for prostate cancer progression and current treatment options

Colin W Hay

Iain J McEwan

Directory of Open Access Journals

The impact of point mutations in the human androgen receptor: classification of mutations on the basis of transcriptional activity.

https://aura.abdn.ac.uk/bitstream/2164/2380/1/Hay_2012_PLoS_One_7.pdf

The impact of point mutations in the human androgen receptor : classification of mutations on the basis of transcriptional activity

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