Global analysis of transcription in castration-resistant prostate cancer cells uncovers active enhancers and direct androgen receptor targets.

Androgen receptor (AR) is a male sex steroid-activated transcription factor (TF) that plays a critical role in prostate cancers, including castration-resistant prostate cancers (CRPC) that typically express amplified levels of the AR. CRPC-derived VCaP cells display an excessive number of chromatin AR-binding sites (ARBs) most of which localize to distal inter- or intragenic regions. Here, we analyzed direct transcription programs of the AR in VCaP cells using global nuclear run-on sequencing (GRO-seq) and integrated the GRO-seq data with the ARB and VCaP cell-specific TF-binding data.

A new vertebrate SUMO enzyme family reveals insights into SUMO-chain assembly.

SUMO chains act as stress-induced degradation tags or repair factor-recruiting signals at DNA lesions. Although E1 activating, E2 conjugating and E3 ligating enzymes efficiently assemble SUMO chains, specific chain-elongation mechanisms are unknown. E4 elongases are specialized E3 ligases that extend a chain but are inefficient in the initial conjugation of the modifier.

Global SUMOylation on active chromatin is an acute heat stress response restricting transcription.

Background: Cells have developed many ways to cope with external stress. One distinctive feature in acute proteotoxic stresses, such as heat shock (HS), is rapid post-translational modification of proteins by SUMOs (small ubiquitin-like modifier proteins; SUMOylation). While many of the SUMO targets are chromatin proteins, there is scarce information on chromatin binding of SUMOylated proteins in HS and the role of chromatin SUMOylation in the regulation of transcription.

Nuclear mobility and activity of FOXA1 with androgen receptor are regulated by SUMOylation.

Forkhead box (FOX) protein A1 has been dubbed a pioneer transcription factor because it binds target sites in DNA, thereby displacing nucleosomes to loosen chromatin and facilitating steroid receptor DNA binding nearby. FOXA1 is an important regulator of prostate development, collaborating with androgen receptor (AR). Post-translational modifications regulating FOXA1 are thus far poorly understood.

SUMOylation modulates the transcriptional activity of androgen receptor in a target gene and pathway selective manner.

Androgen receptor (AR) plays an important regulatory role in prostate cancer. AR's transcriptional activity is regulated by androgenic ligands, but also by post-translational modifications, such as SUMOylation. To study the role of AR SUMOylation in genuine chromatin environment, we compared androgen-regulated gene expression and AR chromatin occupancy in PC-3 prostate cancer cell lines stably expressing wild-type (wt) or doubly SUMOylation site-mutated AR (AR-K386R,K520R).

Prostaglandin 15d-PGJ(2) inhibits androgen receptor signaling in prostate cancer cells.

Androgen signaling, in particular overexpression of the androgen receptor (AR), is critical for the growth and progression of prostate cancer. Because the AR is amenable to targeting by small-molecule inhibitors, it remains the major druggable target for the advanced disease. Inflammation has also been implicated in the cancerous growth in the prostate.

Dynamic SUMOylation is linked to the activity cycles of androgen receptor in the cell nucleus.

Despite of the progress in the molecular etiology of prostate cancer, the androgen receptor (AR) remains the major druggable target for the advanced disease. In addition to hormonal ligands, AR activity is regulated by posttranslational modifications. Here, we show that androgen induces SUMO-2 and SUMO-3 (SUMO-2/3) modification (SUMOylation) of the endogenous AR in prostate cancer cells, which is also reflected in the chromatin-bound receptor.

Analysis of androgen receptor SUMOylation.

Androgen receptor (AR) is a ligand-controlled transcription factor that is deregulated and therefore targeted in prostate cancer. In addition to androgens, AR is regulated by post-translational modifications (PTMs). SUMOylation, conjugation of small ubiquitin-related modifier (SUMO) protein 1, 2, or 3, is a bulky PTM regulating several important physiological processes.

Quantitative test for sensory hand symptoms based on mechanoreceptor-specific vibrotactile thresholds.

A vibrotactile test for assessing the presence or absence of sensory symptoms in the hand has been developed from thresholds believed mediated by Merkel disks and Meissner corpuscles at the fingertips. It is constructed from the summed differences between the thresholds recorded at the fingertip of an individual and the mean values of the threshold for healthy persons at the same stimulation frequencies. The summed normalized threshold shift, TS(Sum(SD)), is shown to be related to reports by subjects of numbness and pain using three statistical tests for evaluating the significance of associations in 2x2 contingency tables.

Vibration-induced hearing loss: mechanical and physiological aspects.

Hypothesis: The sensorineural hearing loss (HL) after middle ear surgery has been explained by the noise generated by drilling, without considering the vibration generated by the burr.

Background: The role of temporal bone vibration in the etiology of the HL was evaluated.

Methods: An electromagnetic shaker was used to vibrate the bony external ear canal of guinea pigs at different frequencies ranging from 32 to 1,000 Hz and at intensities ranging from 4.

Hand-arm vibration syndrome with use of anti-vibration chain saws: 19-year follow-up study of forestry workers.

Objectives: Hand-arm vibration syndrome (HAVS) consists of vascular and neurological component. Musculoskeletal component has not been delineated yet. In the present follow-up study, we evaluated the prevalence of HAVS and the cumulative exposure to vibration among a cohort of forestry workers.

Vibration induced hearing loss in guinea pig cochlea: expression of TNF-alpha and VEGF.

Transcranial vibration was applied for seven animals at a frequency of 250 Hz for 15 min, and five animals were used as normal controls to investigate cellular and molecular mechanism linked to vibration-induced hearing loss in animal model. Compound action potential (CAP) thresholds were measured by round window niche electrode. The expression of tumour necrosis factor alpha (TNF-alpha) and its receptors (TNF R1, TNF R2), vascular endothelium growth factor (VEGF) and its receptors (VEGF R1, VEGF R2) were analysed by immunohistochemistry.