ArticleInternational journal of environmental research and public health2015
Hot Spot Mutation in TP53 (R248Q) Causes Oncogenic Gain-of-Function Phenotypes in a Breast Cancer Cell Line Derived from an African American patient.
Article in International journal of environmental research and public health, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 22 citations in OpenAlex.
- Activation of TP53 target genes in the primary response of triple-negative breast cancer cells to doxorubicin treatment.Scientific reports · 2025Article
- Oxidative Stress-Responsive 1 Kinase Catalytic Activity Promotes Triple Negative Breast Cancer Oncogenic Potential.ACS pharmacology & translational science · 2025Article
- Autocrine Motility Factor and Its Peptide Derivative Inhibit Triple-Negative Breast Cancer by Regulating Wound Repair, Survival, and Drug Efflux.International journal of molecular sciences · 2024Article
- MILIP Binding to tRNAs Promotes Protein Synthesis to Drive Triple-Negative Breast Cancer.Cancer research · 2024Article
- The C-terminus of Gain-of-Function Mutant p53 R273H Is Required for Association with PARP1 and Poly-ADP-Ribose.Molecular cancer research : MCR · 2022Article
- Review
- Gain-of-function hot spot mutant p53Translational oncology · 2021Article
- Comprehensive genomic profile of cholangiocarcinomas in China.Oncology letters · 2020Article
- Targeted Chinese Medicine Delivery by A New Family of Biodegradable Pseudo-Protein Nanoparticles for Treating Triple-Negative Breast Cancer:Frontiers in oncology · 2020Article
- Inhibition of APE1-endonuclease activity affects cell metabolism in colon cancer cells via a p53-dependent pathway.DNA repair · 2019Article
- Gain-of-function mutant p53: history and speculation.Journal of molecular cell biology · 2019Review
- APE1 and NPM1 protect cancer cells from platinum compounds cytotoxicity and their expression pattern has a prognostic value in TNBC.Journal of experimental & clinical cancer research : CR · 2019Article
- Dihydroartemisinin Sensitizes Mutant p53 (R248Q)-Expressing Hepatocellular Carcinoma Cells to Doxorubicin by Inhibiting P-gp Expression.BioMed research international · 2019Article
- Mutant TP53 modulates metastasis of triple negative breast cancer through adenosine A2b receptor signaling.Oncotarget · 2018Article
- Effective treatment of a platinum-resistant cutaneous squamous cell carcinoma case by EGFR pathway inhibition.Molecular and clinical oncology · 2018Article
- Alterations in expression levels of genes in p53-related pathways determined using RNA-Seq analysis in patients with breast cancer following CIK therapy.Oncology letters · 2017Article
- Progression inference for somatic mutations in cancer.Heliyon · 2017Article
- Reversible p53 inhibition prevents cisplatin ototoxicity without blocking chemotherapeutic efficacy.EMBO molecular medicine · 2017Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
African American (AA) breast cancer patients often have triple negative breast cancer (TNBC) that contains mutations in the TP53 gene. The point mutations at amino acid residues R273 and R248 both result in oncogenic gain-of-function (GOF) phenotypes. Expression of mutant p53 (mtp53) R273H associates with increased cell elasticity, survival under serum deprivation conditions, and increased Poly (ADP ribose) polymerase 1 (PARP1) on the chromatin in the AA-derived TNBC breast cancer cell line MDA-MB-468. We hypothesized that GOF mtp53 R248Q expression could stimulate a similar phenotype in the AA-derived TNBC cell line HCC70. To test this hypothesis we depleted the R248Q protein in the HCC70 cell line using shRNA-mediated knockdown. Using impedance-based real-time analysis we correlated the expression of mtp53 R248Q with increased cell deformability. We also documented that depletion of mtp53 R248Q increased PARP1 in the cytoplasm and decreased PARP1 on the chromatin. We conclude that in the AA-derived TNBC HCC70 cells mtp53 R248Q expression results in a causative tumor associated phenotype. This study supports using the biological markers of high expression of mtp53 R273H or R248Q as additional diagnostics for TNBC resistant subtypes often found in the AA community. Each mtp53 protein must be considered separately and this work adds R248Q to the increasing list of p53 mutations that can be used for diagnostics and drug targeting. Here we report that when R248Q mtp53 proteins are expressed in TNBC, then targeting the gain-of-function pathways may improve treatment efficacy.
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