ArticleOncogene2002
Novel gain of function activity of p53 mutants: activation of the dUTPase gene expression leading to resistance to 5-fluorouracil.
Article in Oncogene, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
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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.
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Who cites it
36 citing papers in PubMed, 104 citations in OpenAlex.
- A kinetically inert platinum antitumor agent overcomes mutant p53-driven chemoresistance via oxidative stress-mediated DNA damage.Medical oncology (Northwood, London, England) · 2026Article
- From regulation to deregulation of p53 in hematologic malignancies: implications for diagnosis, prognosis and therapy.Biomarker research · 2024Review
- p53 activation enhances the sensitivity of non-small cell lung cancer to the combination of SH003 and docetaxel by inhibiting de novo pyrimidine synthesis.Cancer cell international · 2024Article
- Stabilizing and upregulating Axin with tankyrase inhibitor reverses 5-fluorouracil chemoresistance and proliferation by targeting the WNT/caveolin-1 axis in colorectal cancer cells.Cancer gene therapy · 2022Article
- Review
- Deoxythymidylate Kinase as a Promising Marker for Predicting Prognosis and Immune Cell Infiltration of Pan-cancer.Frontiers in molecular biosciences · 2022Article
- Review
- Review
- A non-proliferative role of pyrimidine metabolism in cancer.Molecular metabolism · 2020Review
- Gain-of-Function Mutant p53: All the Roads Lead to Tumorigenesis.International journal of molecular sciences · 2019Review
- Exosomal transfer of p-STAT3 promotes acquired 5-FU resistance in colorectal cancer cells.Journal of experimental & clinical cancer research : CR · 2019Article
- Control of Nucleotide Metabolism Enables Mutant p53's Oncogenic Gain-of-Function Activity.International journal of molecular sciences · 2017Review
- Mutant p53 stimulates cell invasion through an interaction with Rad21 in human ovarian cancer cells.Scientific reports · 2017Article
- Transcriptional Regulation by Wild-Type and Cancer-Related Mutant Forms of p53.Cold Spring Harbor perspectives in medicine · 2017Review
- p53 in the mitochondria, as a trans-acting protein, provides error-correction activities during the incorporation of non-canonical dUTP into DNA.Oncotarget · 2016Article
- Oncogenic Mutant p53 Gain of Function Nourishes the Vicious Cycle of Tumor Development and Cancer Stem-Cell Formation.Cold Spring Harbor perspectives in medicine · 2016Review
- A rare DNA contact mutation in cancer confers p53 gain-of-function and tumor cell survival via TNFAIP8 induction.Molecular oncology · 2016Article
- Predictive biomarkers in precision medicine and drug development against lung cancer.Chinese journal of cancer · 2015Review
- Pharmacogenetics research on chemotherapy resistance in colorectal cancer over the last 20 years.World journal of gastroenterology · 2014Review
- Mutant p53 in cancer: new functions and therapeutic opportunities.Cancer cell · 2014Review
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutated forms of p53 are often expressed in a variety of human tumors. In addition to loss of function of the p53 tumor suppressor, mutant p53s contribute to malignant process by acquisition of novel functions that enhance transformed properties of cells and resistance to anticancer therapy in vitro, and increase tumorigenecity, invasiveness and metastatic ability in vivo. Searching for genes that change expression in response to p53 gain of function mutants may give a clue to the mechanisms underlying their oncogenic effects. Recently by subtraction hybridization cloning we found that the dUTPase gene is transcriptionally upregulated in p53-null mouse fibroblasts expressing the exogenous human tumor-derived His175 p53 mutant. Here we show that conditional expression of His175 and Trp248 hot-spot p53 mutants in p53-negative mouse 10(1) fibroblasts and human SK-OV3 and H1299 tumor cells results in increase in dUTPase gene transcription, an important marker predicting the efficacy of cancer therapy with fluoropyrimidine drugs. Using tetracycline-regulated retroviral vectors for conditional expression of p53 mutants, we found that transcription of the dUTPase gene is increased within 24 h after tetracycline withdrawal, and the cells acquire higher resistance to 5-FU. Additional inactivation of the N-terminal transcription activation domain of mutant p53 (substitutions in amino-acid residues 22 and 23) results in abrogation of both induction of dUTPase transcripts and 5-FU resistance.
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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.