ArticleEuropean journal of cancer (Oxford, England : 1990)2014
Inhibition of c-Src blocks oestrogen-induced apoptosis and restores oestrogen-stimulated growth in long-term oestrogen-deprived breast cancer cells.
Article in European journal of cancer (Oxford, England : 1990), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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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
30 citing papers in PubMed, 42 citations in OpenAlex.
- Revisiting Estrogen for the Treatment of Endocrine-Resistant Breast Cancer: Novel Therapeutic Approaches.Cancers · 2023Review
- Estrogen Receptor and the Unfolded Protein Response: Double-Edged Swords in Therapy for Estrogen Receptor-Positive Breast Cancer.Targeted oncology · 2022Review
- PERK, Beyond an Unfolded Protein Response Sensor in Estrogen-Induced Apoptosis in Endocrine-Resistant Breast Cancer.Molecular cancer research : MCR · 2022Review
- Obesity and endocrine therapy resistance in breast cancer: Mechanistic insights and perspectives.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2022Review
- Estrogen Receptor Complex to Trigger or Delay Estrogen-Induced Apoptosis in Long-Term Estrogen Deprived Breast Cancer.Frontiers in endocrinology · 2022Review
- Turning scientific serendipity into discoveries in breast cancer research and treatment: a tale of PhD students and a 50-year roaming tamoxifen team.Breast cancer research and treatment · 2021Review
- Simulated Microgravity Influences VEGF, MAPK, and PAM Signaling in Prostate Cancer Cells.International journal of molecular sciences · 2020Article
- Host Src controls gallid alpha herpesvirus 1 intercellular spread in a cellular fatty acid metabolism-dependent manner.Virology · 2019Article
- Suppression of Nuclear Factor-κB by Glucocorticoid Receptor Blocks Estrogen-Induced Apoptosis in Estrogen-Deprived Breast Cancer Cells.Molecular cancer therapeutics · 2019Article
- Estrogen therapy induces an unfolded protein response to drive cell death in ER+ breast cancer.Molecular oncology · 2019Article
- New insights into acquired endocrine resistance of breast cancer.Cancer drug resistance (Alhambra, Calif.) · 2019Article
- Targeting Peroxisome Proliferator-Activated Receptor γ to Increase Estrogen-Induced Apoptosis in Estrogen-Deprived Breast Cancer Cells.Molecular cancer therapeutics · 2018Article
- Endoxifen, 4-Hydroxytamoxifen and an Estrogenic Derivative Modulate Estrogen Receptor Complex Mediated Apoptosis in Breast Cancer.Molecular pharmacology · 2018Article
- A unifying biology of sex steroid-induced apoptosis in prostate and breast cancers.Endocrine-related cancer · 2018Review
- Genome-Wide Gene Expression Analysis Identifies the Proto-oncogene Tyrosine-Protein Kinase Src as a Crucial Virulence Determinant of Infectious Laryngotracheitis Virus in Chicken Cells.Journal of virology · 2016Article
- The molecular, cellular and clinical consequences of targeting the estrogen receptor following estrogen deprivation therapy.Molecular and cellular endocrinology · 2015Review
- Integration of Downstream Signals of Insulin-like Growth Factor-1 Receptor by Endoplasmic Reticulum Stress for Estrogen-Induced Growth or Apoptosis in Breast Cancer Cells.Molecular cancer research : MCR · 2015Article
- Estrogen receptor mutations found in breast cancer metastases integrated with the molecular pharmacology of selective ER modulators.Journal of the National Cancer Institute · 2015Article
- Mechanisms of aromatase inhibitor resistance.Nature reviews. Cancer · 2015Review
- Proven value of translational research with appropriate animal models to advance breast cancer treatment and save lives: the tamoxifen tale.British journal of clinical pharmacology · 2015Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
purposeOur publications demonstrate that physiological concentrations of oestrogen (E2) induce endoplasmic reticulum and oxidative stress which finally result in apoptosis in E2-deprived breast cancer cells, MCF-7:5C. c-Src is involved in the process of E2-induced stress. To mimic the clinical administration of c-Src inhibitors, we treated cells with either E2, a c-Src inhibitor PP2, or the combination for 8 weeks to further explore the apoptotic potential of the c-Src inhibitor and E2 on MCF-7:5C cells.
methodsProtein levels of receptors and signalling pathways were examined by immunoblotting. Expression of mRNA was detected through real-time polymerase chain reaction (PCR). Cell cycles were analysed by flow cytometry.
resultsLong-term treatment with PP2 alone or E2 alone decreased cell growth. In contrast, a combination of PP2 and E2 blocked apoptosis and the resulting cell line (MCF-7:PF) was unique, as they grew vigorously in culture with physiological levels of E2, which could be blocked by the pure antioestrogen ICI182,780. One major change was that PP2 collaborated with E2 to increase the level of insulin-like growth factor-1 receptor beta (IGF-1Rβ). Blockade of IGF-1Rβ completely abolished E2-stimulated growth in MCF-7:PF cells. Furthermore, combination treatment up-regulated transcription factors, Twist1 and Snail, and repressed E-cadherin expression which made MCF-7:PF cells display a characteristic phenotype of epithelial-mesenchymal transition (EMT).
conclusionsThese data illustrate the role of the c-Src inhibitor to block E2-induced apoptosis and enhance E2-stimulated growth. Caution must be exercised when considering c-Src inhibitors in clinical trials following the development of acquired resistance to aromatase inhibitors, especially in the presence of the patient's own oestrogen.
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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.