ArticlePloS one2014
Complex impacts of PI3K/AKT inhibitors to androgen receptor gene expression in prostate cancer cells.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 36 citations in OpenAlex.
- Investigation of the inhibitory behavior of XFE and mitoxantrone molecules in interaction with AKT1 protein: a molecular dynamics simulation study.Journal of molecular modeling · 2023Article
- Antiandrogenic Effects of a Polyphenol inInternational journal of molecular sciences · 2022Article
- Identification of Potential miRNAs Biomarkers for High-Grade Prostate Cancer by Integrated Bioinformatics Analysis.Pathology oncology research : POR · 2019Article
- Article
- Induction of entosis in prostate cancer cells by nintedanib and its therapeutic implications.Oncology letters · 2019Article
- The Secret Life of Translation Initiation in Prostate Cancer.Frontiers in genetics · 2019Review
- Androgen represses opioid growth factor receptor (OGFR) in human prostate cancer LNCaP cells and OGFR expression in human prostate cancer tissue.American journal of clinical and experimental urology · 2018Article
- Implications of PI3K/AKT inhibition on REST protein stability and neuroendocrine phenotype acquisition in prostate cancer cells.Oncotarget · 2017Article
- Glutamine Transporters Are Targets of Multiple Oncogenic Signaling Pathways in Prostate Cancer.Molecular cancer research : MCR · 2017Article
- AR Signaling and the PI3K Pathway in Prostate Cancer.Cancers · 2017Review
- Oridonin induces GOncology letters · 2017Article
- Combination effect of therapies targeting the PI3K- and AR-signaling pathways in prostate cancer.Oncotarget · 2016Article
- PCA3 long noncoding RNA modulates the expression of key cancer-related genes in LNCaP prostate cancer cells.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Cotargeting Androgen Receptor Splice Variants and mTOR Signaling Pathway for the Treatment of Castration-Resistant Prostate Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2016Article
- Combined AKT and MEK Pathway Blockade in Pre-Clinical Models of Enzalutamide-Resistant Prostate Cancer.PloS one · 2016Article
- Article
- Deletion of NKX3.1 via CRISPR/Cas9 Induces Prostatic Intraepithelial Neoplasia in C57BL/6 Mice.Technology in cancer research & treatmentArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundAndrogen deprivation therapy (ADT) is the first-line treatment to metastatic prostate cancer (PCa). However, sustained expression and function of the androgen receptor (AR) gene contribute to the progression of castration resistant prostate cancers (CRPC). Additionally, tumors can adapt the PI3K/AKT survival pathway to escape ADT. Co-targeting AR and PI3K/AKT signaling has been proposed to be a more effective therapeutic means for CRPC patients. Many clinical trials are ongoing to test whether PI3K/AKT inhibitors are beneficial to PCa patients. However whether these inhibitors have any impacts on the expressions of full length AR (AR-FL) and its splice variant (AR-V7) remains unclear.
methodsFour human prostate cancer cell lines (LNCaP, LNCaP95, VCaP and 22Rv1) with different genetic backgrounds were treated with five PI3K/AKT inhibitors (LY294002, Wortmannin, BKM120, AKTi and AZD5363) and or AKT siRNA. AR and AR-V7 protein and mRNA levels were measured by immunoblotting and real-time PCR assays. AR gene transcription initiation, alternative RNA splicing and AR mRNA degradation rates were also determined.
resultsPI3K/AKT inhibitors had various impacts on AR protein expressions primarily through alterations of AR gene transcription initiation and RNA splicing. However, these effects remained unchanged in the presence RNA silencing of the AKT genes.
conclusionPI3K/AKT inhibitors have off-target effects on AR gene expression in prostate cancer cells, which shall be considered when applying these inhibitors to PCa patients, particularly patients under ADT treatment.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.