ArticleBMC cancer2015
Aurora kinase B is important for antiestrogen resistant cell growth and a potential biomarker for tamoxifen resistant breast cancer.
Article in BMC cancer, 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, 24 citations in OpenAlex.
- Effects of cuproptosis and its application in inflammatory bowel disease (Review).International journal of molecular medicine · 2026Review
- Article
- Aurora B facilitates cholangiocarcinoma progression by stabilizing c-Myc.Animal models and experimental medicine · 2024Article
- Stratification of Tamoxifen Synergistic Combinations for the Treatment of ER+ Breast Cancer.Cancers · 2023Article
- Construction of miRNA-lncRNA-mRNA co-expression network affecting EMT-mediated cisplatin resistance in ovarian cancer.Journal of cellular and molecular medicine · 2022Article
- Cancer stem cells: Culprits in endocrine resistance and racial disparities in breast cancer outcomes.Cancer letters · 2021Article
- Aurora kinases in ovarian cancer.ESMO open · 2020Review
- Inhibition of AURKB, regulated by pseudogeneAmerican journal of cancer research · 2020Article
- Clinical Implications of Chromosomal Instability (CIN) and Kinetochore Abnormalities in Breast Cancers.Molecular diagnosis & therapy · 2019Review
- Article
- Calein C, a Sesquiterpene Lactone Isolated FromFrontiers in pharmacology · 2018Article
- Deguelin, an Aurora B Kinase Inhibitor, Exhibits Potent Anti-Tumor Effect in Human Esophageal Squamous Cell Carcinoma.EBioMedicine · 2017Article
- Protein Kinase Targets in Breast Cancer.International journal of molecular sciences · 2017Review
- A post-translational modification switch controls coactivator function of histone methyltransferases G9a and GLP.EMBO reports · 2017Article
- Racial disparity in survival from estrogen and progesterone receptor-positive breast cancer: implications for reducing breast cancer mortality disparities.Breast cancer research and treatment · 2017Article
- Aurora kinases: novel therapy targets in cancers.Oncotarget · 2017Review
- Expression of transmembrane protein 26 (TMEM26) in breast cancer and its association with drug response.Oncotarget · 2016Article
- Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundResistance to antiestrogen therapy is a major clinical challenge in the treatment of estrogen receptor α (ER)-positive breast cancer. The aim of the study was to explore the growth promoting pathways of antiestrogen resistant breast cancer cells to identify biomarkers and novel treatment targets.
methodsAntiestrogen sensitive and resistant T47D breast cancer cell lines were used as model systems. Parental and fulvestrant resistant cell lines were subjected to a kinase inhibitor library. Kinase inhibitors preferentially targeting growth of fulvestrant resistant cells were identified and the growth inhibitory effect verified by dose-response cell growth experiments. Protein expression and phosphorylation were investigated by western blot analysis. Cell cycle phase distribution and cell death were analyzed by flow cytometry. To evaluate Aurora kinase B as a biomarker for endocrine resistance, immunohistochemistry was performed on archival primary tumor tissue from breast cancer patients who have received adjuvant endocrine treatment with tamoxifen.
resultsThe selective Aurora kinase B inhibitor barasertib was identified to preferentially inhibit growth of fulvestrant resistant T47D breast cancer cell lines. Compared with parental cells, phosphorylation of Aurora kinase B was higher in the fulvestrant resistant T47D cells. Barasertib induced degradation of Aurora kinase B, caused mitotic errors, and induced apoptotic cell death as measured by accumulation of SubG1 cells and PARP cleavage in the fulvestrant resistant cells. Barasertib also exerted preferential growth inhibition of tamoxifen resistant T47D cell lines. Finally, high percentage of Aurora kinase B positive tumor cells was significantly associated with reduced disease-free and overall survival in 261 ER-positive breast cancer patients, who have received tamoxifen as first-line adjuvant endocrine treatment.
conclusionsOur results indicate that Aurora kinase B is a driving factor for growth of antiestrogen resistant T47D breast cancer cell lines, and a biomarker for reduced benefit of tamoxifen treatment. Thus, inhibition of Aurora kinase B, e.g. with the highly selective kinase inhibitor barasertib, could be a candidate new treatment for breast cancer patients with acquired resistance to antiestrogens.
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