| Title |
The BET-inhibitor PFI-1 diminishes AR/AR-V7 signaling in prostate cancer cells
|
|---|---|
| Published in |
World Journal of Urology, June 2018
|
| DOI | 10.1007/s00345-018-2382-8 |
| Pubmed ID | |
| Authors |
Marie C. Hupe, M. Raschid Hoda, Friedemann Zengerling, Sven Perner, Axel S. Merseburger, Marcus V. Cronauer |
| Abstract |
The bromodomain and extra-terminal (BET) family of proteins provides a scaffolding platform for the recruitment and tethering of transcription factors to acetylated chromatin, thereby modulating gene expression. In this study, we evaluated the efficacy of the BET-inhibitor PFI-1 to diminish AR/AR-V7 signaling and proliferation in castration-resistant prostate cancer cells. Prostate-specific antigen and androgen receptor (AR) protein were quantified by means of two commercial ELISAs. Transactivation of the AR, AR-V7 and Q641X was determined by reporter gene assays. Cell proliferation was measured using a colorimetric MTT-assay. PFI-1 dose-dependently inhibited transactivation of full-length AR (non- mutated, i.e., wild-type or point-mutated/promiscuous forms) without affecting their cellular protein levels. Moreover, PFI-1 was active against C-terminally truncated constitutively active ARs like AR-V7 and Q641X. Prostate cancer cells exhibiting a transcriptionally active AR-signaling complex (LNCaP, 22Rv1) were more susceptible to the growth-inhibitory effects than the AR-negative PC-3 cells. The quinazolinone PFI-1 is a highly efficient inhibitor of AR-signaling-competent prostate cancer cells in vitro. PFI-1 could serve as a lead compound for the development of new therapeutics able to block AR/AR-V7 signaling in advanced prostate cancer. |
X Demographics
The data shown below were collected from the profiles of 6 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| France | 1 | 17% |
| United Kingdom | 1 | 17% |
| Germany | 1 | 17% |
| Unknown | 3 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Science communicators (journalists, bloggers, editors) | 2 | 33% |
| Members of the public | 2 | 33% |
| Scientists | 1 | 17% |
| Practitioners (doctors, other healthcare professionals) | 1 | 17% |
Mendeley readers
The data shown below were compiled from readership statistics for 19 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 19 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 4 | 21% |
| Lecturer | 2 | 11% |
| Student > Doctoral Student | 2 | 11% |
| Student > Master | 2 | 11% |
| Student > Bachelor | 1 | 5% |
| Other | 2 | 11% |
| Unknown | 6 | 32% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 5 | 26% |
| Pharmacology, Toxicology and Pharmaceutical Science | 2 | 11% |
| Chemistry | 2 | 11% |
| Biochemistry, Genetics and Molecular Biology | 1 | 5% |
| Psychology | 1 | 5% |
| Other | 3 | 16% |
| Unknown | 5 | 26% |
Attention Score in Context
This research output has an Altmetric Attention Score of 4. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 16 September 2018.
All research outputs
#6,954,875
of 23,094,276 outputs
Outputs from World Journal of Urology
#759
of 2,117 outputs
Outputs of similar age
#119,643
of 328,686 outputs
Outputs of similar age from World Journal of Urology
#26
of 60 outputs
Altmetric has tracked 23,094,276 research outputs across all sources so far. This one has received more attention than most of these and is in the 69th percentile.
So far Altmetric has tracked 2,117 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.1. This one has gotten more attention than average, scoring higher than 63% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 328,686 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 63% of its contemporaries.
We're also able to compare this research output to 60 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 55% of its contemporaries.