ArticlePloS one2013
Identification of mutations in distinct regions of p85 alpha in urothelial cancer.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
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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.
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Who cites it
11 citing papers in PubMed, 17 citations in OpenAlex.
- Article
- Epiplakin1 promotes the progression of esophageal squamous cell carcinoma by activating the PI3K-AKT signaling pathway.Thoracic cancer · 2022Article
- DIPG Harbors Alterations Targetable by MEK Inhibitors, with Acquired Resistance Mechanisms Overcome by Combinatorial Inhibition.Cancer discovery · 2022Article
- Somatic PIK3R1 variation as a cause of vascular malformations and overgrowth.Genetics in medicine : official journal of the American College of Medical Genetics · 2021Article
- Potential Impact of MicroRNA Gene Polymorphisms in the Pathogenesis of Diabetes and Atherosclerotic Cardiovascular Disease.Journal of personalized medicine · 2019Review
- Impact of p85α Alterations in Cancer.Biomolecules · 2019Review
- Patient-derived mutations within the N-terminal domains of p85α impact PTEN or Rab5 binding and regulation.Scientific reports · 2018Article
- Identification of the Binding Sites on Rab5 and p110beta Phosphatidylinositol 3-kinase.Scientific reports · 2017Article
- Impacts of somatic mutations on gene expression: an association perspective.Briefings in bioinformatics · 2017Article
- PIK3CA dependence and sensitivity to therapeutic targeting in urothelial carcinoma.BMC cancer · 2016Article
- p85α is a microRNA target and affects chemosensitivity in pancreatic cancer.The Journal of surgical research · 2015Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Bladder cancers commonly show genetic aberrations in the phosphatidylinositol 3-kinase signaling pathway. Here we have screened for mutations in PIK3R1, which encodes p85α, one of the regulatory subunits of PI3K. Two hundred and sixty-four bladder tumours and 41 bladder tumour cell lines were screened and 18 mutations were detected. Thirteen mutations were in C-terminal domains and are predicted to interfere with the interaction between p85α and p110α. Five mutations were in the BH domain of PIK3R1. This region has been implicated in p110α-independent roles of p85α, such as binding to and altering the activities of PTEN, Rab4 and Rab5. Expression of these mutant BH-p85α forms in mouse embryonic fibroblasts with p85α knockout indicated that all forms, except the truncation mutants, could bind and stabilize p110α but did not increase AKT phosphorylation, suggesting that BH mutations function independently of p110α. In a panel of 44 bladder tumour cell lines, 80% had reduced PIK3R1 mRNA expression relative to normal urothelial cells. This, along with mutation of PIK3R1, may alter BH domain functioning. Our findings suggest that mutant forms of p85α may play an oncogenic role in bladder cancer, not only via loss of ability to regulate p110α but also via altered function of the BH domain.
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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.