ArticleCancer research2009
Activation of the PI3K/AKT pathway induces urothelial carcinoma of the renal pelvis: identification in human tumors and confirmation in animal models.
Article in Cancer research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.
- Guidelines for the welfare and use of animals in cancer research.British journal of cancer · 2010Guideline
- Identification and expression of prognostic-related genes in kidney renal clear cell carcinoma and their possible regulatory mechanisms.Translational andrology and urology · 2024Article
- Emerging Importance of Chemokine Receptor CXCR4 and Its Ligand in Liver Disease.Frontiers in cell and developmental biology · 2021Review
- Low PTEN expression and overexpression of phosphorylated AktOncology letters · 2020Article
- Role of PI3K/AKT pathway in cancer: the framework of malignant behavior.Molecular biology reports · 2020Review
- Article
- Candidate tumor suppressor gene IRF6 is involved in human breast cancer pathogenesis via modulating PI3K-regulatory subunit PIK3R2 expression.Cancer management and research · 2019Article
- Combined inhibition of PI3K and Src kinases demonstrates synergistic therapeutic efficacy in clear-cell renal carcinoma.Oncotarget · 2018Article
- Along with its favorable prognostic role, CLCA2 inhibits growth and metastasis of nasopharyngeal carcinoma cells via inhibition of FAK/ERK signaling.Journal of experimental & clinical cancer research : CR · 2018Article
- Hsa-miR-137, hsa-miR-520e and hsa-miR-590-3p perform crucial roles in Lynch syndrome.Oncology letters · 2016Article
- MicroRNA-214 Reduces Insulin-like Growth Factor-1 (IGF-1) Receptor Expression and Downstream mTORC1 Signaling in Renal Carcinoma Cells.The Journal of biological chemistry · 2016Article
- Article
- Article
- Prognostic Genetic Signatures in Upper Tract Urothelial Carcinoma.Current urology reports · 2016Review
- SPOCK1 Overexpression Confers a Poor Prognosis in Urothelial Carcinoma.Journal of Cancer · 2016Article
- Disruption of tubular Flcn expression as a mouse model for renal tumor induction.Kidney international · 2015Article
- Genetic deletion and pharmacological inhibition of Akt1 isoform attenuates bladder cancer cell proliferation, motility and invasion.European journal of pharmacology · 2015Article
- The role of WNT signalling in urothelial cell carcinoma.Annals of the Royal College of Surgeons of England · 2015Article
- Is 5´-AMP-Activated Protein Kinase Both Jekyll and Hyde in Bladder Cancer?International neurourology journal · 2015Review
- Molecular Analysis of Upper Tract and Bladder Urothelial Carcinoma: Results from a Microarray Comparison.PloS one · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
23 authors at 6 institutions in 4 countries.
Funding
Abstract
Urothelial carcinoma of the renal pelvis is a deadly disease with an unclear tumorigenic mechanism. We conducted gene expression profiling on a set of human tumors of this type and identified a phosphatidylinositol 3-kinase (PI3K)/AKT activation expression signature in 76.9% (n = 13) of our samples. Sequence analysis found both activating mutations of PIK3CA (13.6%, n = 22) and loss of heterozygosity at the PTEN locus (25%, n = 8). In contrast, none of the other subtypes of kidney neoplasms (e.g., clear-cell renal cell carcinoma) harbored PIK3CA mutations (n = 87; P < 0.001). Immunohistochemical analysis of urothelial carcinoma samples found loss of PTEN protein expression (36.4%, n = 11) and elevation of phosphorylated mammalian target of rapamycin (mTOR; 63.6%, n = 11). To confirm the role of the PI3K/AKT pathway in urothelial carcinoma, we generated mice containing biallelic inactivation of Pten in the urogenital epithelia. These mice developed typical renal pelvic urothelial carcinomas, with an incidence of 57.1% in mice older than 1 year. Laser capture microdissection followed by PCR confirmed the deletion of Pten exons 4 and 5 in the animal tumor cells. Immunohistochemical analyses showed increased phospho-mTOR and phospho-S6K levels in the animal tumors. Renal lymph node metastases were found in 15.8% of the animals with urothelial carcinoma. In conclusion, we identified and confirmed an important role for the PI3K/AKT pathway in the development of urothelial carcinoma and suggested that inhibitors of this pathway (e.g., mTOR inhibitor) may serve as effective therapeutic agents.
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.