ArticlePloS one2013
Luminal breast cancer cell lines overexpressing ZNF703 are resistant to tamoxifen through activation of Akt/mTOR signaling.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 49 citations in OpenAlex.
- Genomic Profiling of Premenopausal HR+ and HER2- Metastatic Breast Cancer by Circulating Tumor DNA and Association of Genetic Alterations With Therapeutic Response to Endocrine Therapy and Ribociclib.JCO precision oncology · 2021Trial
- βFrontiers in immunology · 2024Article
- Large-Scale Machine Learning Analysis Reveals DNA Methylation and Gene Expression Response Signatures for Gemcitabine-Treated Pancreatic Cancer.Health data science · 2024Article
- Insights into the pleiotropic roles of ZNF703 in cancer.Heliyon · 2023Review
- The Influence of Race/Ethnicity on the Transcriptomic Landscape of Uterine Fibroids.International journal of molecular sciences · 2023Article
- Article
- Andrographolide Exhibits Anticancer Activity against Breast Cancer Cells (MCF-7 and MDA-MB-231 Cells) through Suppressing Cell Proliferation and Inducing Cell Apoptosis via Inactivation of ER-α Receptor and PI3K/AKT/mTOR Signaling.Molecules (Basel, Switzerland) · 2022Article
- ZNF703 promotes triple-negative breast cancer cells through cell-cycle signaling and associated with poor prognosis.BMC cancer · 2022Article
- Prognostic Roles of ZNF703 and SMAD4 Expression in Patients with Papillary Thyroid Cancer and Association with Nodal Metastasis.Indian journal of surgical oncology · 2022Article
- Uterine perivascular epithelioid tumors (PEComas) with lung metastasis showed good responses to mTOR and VEGFR inhibitors: A case report.Frontiers in oncology · 2022Article
- Review
- Biomarkers in Breast Cancer: An Integrated Analysis of Comprehensive Genomic Profiling and PD-L1 Immunohistochemistry Biomarkers in 312 Patients with Breast Cancer.The oncologist · 2020Article
- 8p11.23 Amplification in Breast Cancer: Molecular Characteristics, Prognosis and Targeted Therapy.Journal of clinical medicine · 2020Article
- Silencing of zinc finger protein 703 inhibits medullary thyroid carcinoma cell proliferationOncology letters · 2020Article
- Article
- Article
- Differential Expression and Pathway Analysis in Drug-Resistant Triple-Negative Breast Cancer Cell Lines Using RNASeq Analysis.International journal of molecular sciences · 2018Article
- Copy number changes at 8p11-12 predict adverse clinical outcome and chemo- and radiotherapy response in breast cancer.Oncotarget · 2018Article
- Genomic Landscape and Endocrine-Resistant Subgroup in Estrogen Receptor-Positive, Progesterone Receptor-Negative, and HER2-Negative Breast Cancer.Theranostics · 2018Article
- Overexpression of ZNF703 facilitates tumorigenesis and predicts unfavorable prognosis in patients with cholangiocarcinoma.Oncotarget · 2016Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSelective estrogen receptor modulators, such as tamoxifen, play a pivotal role in the treatment of luminal-type breast cancer. However, in clinical applications, nearly half of breast cancer patients are insensitive to tamoxifen, a small number of whom have early recurrence or disease progression when receiving tamoxifen. The underlying mechanism of this resistance has not been determined. ZNF703 is a novel oncogene in the 15% of breast cancers that harbor 8p12 amplifications. Therefore, the goal of our study was to explore the role of ZNF703 in tamoxifen resistance. METHODOLOGY/PRINCIPAL
findingsWe used immunohistochemistry techniques to examine ZNF703 expression in stage I-III primary breast cancer specimens and found a positive expression rate of 91.3%. All patients were divided into either high or low ZNF703 expression groups. We found that high ZNF703 expression mainly occurred in ER+ and PR+ breast cancers. Furthermore, 4-hydroxytamoxifen had different modes of action in breast cancer cell lines with high or low ZNF703 expression. ZNF703 overexpression in MCF-7 breast cancer cells activated the Akt/mTOR signaling pathway, downregulated ERα, and reduced the antitumor effect of tamoxifen. Low-dose tamoxifen did not suppress, but rather, stimulated the growth of cells overexpressing ZNF703. ZNF703 knockdown in MDA-MB-134 and HCC1500 luminal B-type breast cancer cell lines by siRNA significantly decreased survival rates when cells were treated with tamoxifen. Furthermore, targeting ZNF703 with a mTOR inhibitor increased the inhibitory effects of tamoxifen in ZNF703-overexpressing cells. CONCLUSION/SIGNIFICANCE: Our study suggests that ZNF703 expression levels may predict tamoxifen sensitivity. Tamoxifen should be administered with caution to those patients bearing tumors with ZNF703 overexpression. However, large clinical trials and prospective clinical studies are needed to verify these results.
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