ArticleOncogene2004
p53 deficiency provokes urothelial proliferation and synergizes with activated Ha-ras in promoting urothelial tumorigenesis.
Article in Oncogene, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 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
28 citing papers in PubMed, 57 citations in OpenAlex.
- Bioprinted research models of urological malignancy.Exploration (Beijing, China) · 2024Review
- Review
- Intensity of Nuclear Staining for Ki-67, p53 and Survivin as a New Prognostic Factor in Non-muscle Invasive Bladder Cancer.Pathology oncology research : POR · 2020Article
- Up-regulated ENO1 promotes the bladder cancer cell growth and proliferation via regulating β-catenin.Bioscience reports · 2019Article
- Insights from animal models of bladder cancer: recent advances, challenges, and opportunities.Oncotarget · 2017Review
- Proceedings of the 3rd Annual Albert Institute for Bladder Cancer Research Symposium.Bladder cancer (Amsterdam, Netherlands) · 2017Article
- Ras Regulates Rb via NORE1A.The Journal of biological chemistry · 2016Article
- Targeting mTOR and p53 Signaling Inhibits Muscle Invasive Bladder Cancer In Vivo.Cancer prevention research (Philadelphia, Pa.) · 2016Article
- The role of WNT signalling in urothelial cell carcinoma.Annals of the Royal College of Surgeons of England · 2015Article
- Oncogenic HRAS Activates Epithelial-to-Mesenchymal Transition and Confers Stemness to p53-Deficient Urothelial Cells to Drive Muscle Invasion of Basal Subtype Carcinomas.Cancer research · 2015Article
- Single and Multiple Gene Manipulations in Mouse Models of Human Cancer.Cancer growth and metastasis · 2015Review
- Modelling bladder cancer in mice: opportunities and challenges.Nature reviews. Cancer · 2015Review
- Bladder cancers arise from distinct urothelial sub-populations.Nature cell biology · 2014Article
- When urothelial differentiation pathways go wrong: implications for bladder cancer development and progression.Urologic oncology · 2013Review
- Decreased tumorigenesis and mortality from bladder cancer in mice lacking urothelial androgen receptor.The American journal of pathology · 2013Article
- Simultaneous activation of Kras and inactivation of p53 induces soft tissue sarcoma and bladder urothelial hyperplasia.PloS one · 2013Article
- Exploring molecular genetics of bladder cancer: lessons learned from mouse models.Disease models & mechanisms · 2012Review
- Urothelial tumor initiation requires deregulation of multiple signaling pathways: implications in target-based therapies.Carcinogenesis · 2012Article
- Loss of p53 and acquisition of angiogenic microRNA profile are insufficient to facilitate progression of bladder urothelial carcinoma in situ to invasive carcinoma.The Journal of biological chemistry · 2011Article
- Personalized therapy for urothelial cancer: review of the clinical evidence.Clinical investigation · 2011Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Mutation and deletion of the p53 tumor suppressor gene are arguably the most prevalent among the multiple genetic alterations found in human bladder cancer, but these p53 defects are primarily associated with the advanced diseases, and their roles in bladder tumor initiation and in synergizing with oncogenes in tumor progression have yet to be defined. Using the mouse uroplakin II gene promoter, we have targeted into urothelium of transgenic mice a dominant-negative mutant of p53 that lacks the DNA-binding domain but retains the tetramerization domain. Urothelium-expressed p53 mutant binds to and stabilizes the endogenous wild-type p53, induces nuclear abnormality, hyperplasia and occasionally dysplasia, without eliciting frank carcinomas. Concurrent expression of the p53 mutant with an activated Ha-ras, the latter of which alone induces urothelial hyperplasia, fails to accelerate tumor formation. In contrast, the expression of the activated Ha-ras in the absence of p53, as accomplished by crossing the activated Ha-ras transgenic mice with the p53 knockout mice, results in early-onset bladder tumors that are either low-grade superficial papillary or high grade in nature. These results provide the first in vivo experimental evidence that p53 deficiency predisposes the urothelium to hyperproliferation, but is insufficient for bladder tumorigenesis; that the mere reduction of p53 dosage, as produced in transgenic mice expressing the dominant-negative p53 or in heterozygous p53 knockouts, is incapable of synergizing with Ha-ras to induce bladder tumors; and that the complete loss of p53 is a prerequisite for collaborating with activated Ha-ras to promote bladder tumorigenesis.
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.