ArticleBMC cancer2018
Mutant p53 gain of function induces HER2 over-expression in cancer cells.
Article in BMC cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Human Papillomavirus 16 E2 as an Apoptosis-Inducing Protein for Cancer Treatment: A Systematic Review.International journal of molecular sciences · 2022Pooled it
- Features of tumor microenvironment in HER2-positive urothelial carcinoma and its implications for immunotherapy resistance.BMC cancer · 2026Article
- Next-Generation Sequencing Reveals a Diagnostic and Prognostic Role of theInternational journal of molecular sciences · 2025Article
- Case series of Li-Fraumeni syndrome: carcinogenic mechanisms in breast cancer with TP53 pathogenic variant carriers.Breast cancer (Tokyo, Japan) · 2024Article
- AVERON notebook to discover actionable cancer vulnerabilities enabled by neomorph protein-protein interactions.iScience · 2024Article
- Variation Analysis in Premenopausal and Postmenopausal Breast Cancer Cases.Journal of personalized medicine · 2024Article
- Challenging Tumor Heterogeneity with HER2, p16 and Somatostatin Receptor 2 Expression in a Case of EBV-Associated Lymphoepithelial Carcinoma of the Salivary Gland.Head and neck pathology · 2023Article
- Article
- Review
- Antitumor activity of the protein kinase inhibitor 1-(β-D-2'-deoxyribofuranosyl)-4,5,6,7-tetrabromo- 1H-benzimidazole in breast cancer cell lines.BMC cancer · 2022Article
- Interaction between HER2 and ATM predicts poor survival in bladder cancer patients.Journal of cellular and molecular medicine · 2022Article
- HER2-enriched subtype and novel molecular subgroups drive aromatase inhibitor resistance and an increased risk of relapse in early ER+/HER2+ breast cancer.EBioMedicine · 2022Article
- Multi-Gene Mutation Profiling by Targeted Next-Generation Sequencing in Premenopausal Breast Cancer.Genes · 2022Article
- TP53 R273C Mutation Is Associated With Poor Prognosis in LGG Patients.Frontiers in genetics · 2022Article
- Review
- Gain-of-function hot spot mutant p53Translational oncology · 2021Article
- Article
- Association of MicroRNA-21 with p53 at Mutant Sites R175H and R248Q, Clinicopathological Features, and Prognosis of NSCLC.Molecular therapy oncolytics · 2020Article
- Suggested application of HER2+ breast tumor phenotype for germline TP53 variant classification within ACMG/AMP guidelines.Human mutation · 2020Article
- Molecular Bases of Mechanisms Accounting for Drug Resistance in Gastric Adenocarcinoma.Cancers · 2020Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundHER2 over-expression is related with a poor prognosis in patients with invasive breast cancer tumors. Clinical associations have reported that somatic mutations of p53 more frequently detected in cases of sporadic breast cancer of the HER2 subtypes, besides a high percentage of HER2-amplifying tumors carry germline mutations of p53. The mechanisms responsible for the acquisition of oncogenic functions of p53 mutant proteins (mtp53), known as Gain of Function (GOF), over HER2 expression have not been reported. The objective of this study was to evaluate a possible relationship between p53 mutants and HER2 regulation.
methodsHER2 expression (transcription and protein), as well as HER2 protein stabilization have been evaluated after inducing or silencing of p53 mutants' expression in cell lines. Finally, we evaluated the interaction of the p53 mutants over the HER2 receptor promoter.
resultsHigher HER2 expression in cell lines harboring endogenous mtp53 compared with wt or null expression of p53 cell lines. Transfection of p53 mutants (R248Q and R273C) in cell lines increased the expression of HER2. Silencing of p53 mutants, decrease HER2 expression. The p53 mutants R248Q and R273C significantly increase the luciferase activity on the HER2 promoter, and both mutants also promote acetylation of H3 and H4 histones binding in it.
conclusionsThese findings show for the first time that p53 mutants induce over-expression of HER2 at transcriptional level of the HER2 protein. Our results could have clinical implications in breast cancer and other types of cancer where HER2 is over-expressed and used as a therapy target.
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