scholarly journals Elucidating the novel BRCA1 function as a non-genomic metabolic restraint in ER-positive breast cancer cell lines

Oncotarget ◽  
2018 ◽  
Vol 9 (71) ◽  
pp. 33562-33576 ◽  
Author(s):  
Moses Koobotse ◽  
Jeff Holly ◽  
Claire Perks
Nutrients ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 237 ◽  
Author(s):  
Sylvain Lecomte ◽  
Florence Demay ◽  
Thu Ha Pham ◽  
Solenn Moulis ◽  
Théo Efstathiou ◽  
...  

The flavone apigenin and the mycotoxin zearalenone are two major compounds found in the human diet which bind estrogen receptors (ERs), and therefore influence ER activity. However, the underlying mechanisms are not well known. To unravel the molecular mechanisms that could explain the differential effect of zearalenone and apigenin on ER-positive breast cancer cell proliferation, gene-reporter assays, chromatin immunoprecipitation (ChIP) experiments, proliferation assays and transcriptomic analysis were performed. We found that zearalenone and apigenin transactivated ERs and promoted the expression of estradiol (E2)-responsive genes. However, zearalenone clearly enhanced cellular proliferation, while apigenin appeared to be antiestrogenic in the presence of E2 in both ER-positive breast cancer cell lines, MCF-7 and T47D. The transcriptomic analysis showed that both compounds regulate gene expression in the same way, but with differences in intensity. Two major sets of genes were identified; one set was linked to the cell cycle and the other set was linked to stress response and growth arrest. Our results show that the transcription dynamics in gene regulation induced by apigenin were somehow different with zearalenone and E2 and may explain the differential effect of these compounds on the phenotype of the breast cancer cell. Together, our results confirmed the potential health benefit effect of apigenin, while zearalenone appeared to be a true endocrine-disrupting compound.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 632-632 ◽  
Author(s):  
Alexandra Canonici ◽  
Kasper Pedersen ◽  
Brigid Browne ◽  
Martina McDermott ◽  
Naomi Walsh ◽  
...  

632 Background: Trastuzumab and lapatinib have been shown to significantly improve the prognosis for HER2 positive breast cancer patients. However, resistance is a significant clinical problem. The aim of this study is to assess the activity of afatinib, an irreversible pan-HER tyrosine kinase inhibitor, in HER2 overexpressing breast cancer cell lines, including trastuzumab and/or lapatinib resistant cells. Methods: Using proliferation assays, the effect of afatinib was assessed alone and in combination with trastuzumab in HER2 positive cell lines. The effect of afatinib on HER2, Erk and Akt was determined by immunoblotting. Results: The eight HER2 positive breast cancer cell lines tested, including trastuzumab and/or lapatinib resistant cells, responded to afatinib with IC50values ranging from 5 to 80 nM. The combination of afatinib and trastuzumab was additive in four trastuzumab sensitive cell lines and one model of acquired trastuzumab resistant HER2 positive breast cancer. In the remaining three trastuzumab and/or lapatinib resistant cell lines, combined treatment with trastuzumab and afatinib showed no enhancement compared to afatinib alone. Finally, afatinib decreased the phosphorylation of HER2 and Erk in all cell lines tested. Conclusions: Our results suggest that afatinib has activity in HER2 positive breast cancer, including trastuzumab and/or lapatinib resistant breast cancer. We also demonstrate that afatinib in combination with trastuzumab may be more effective than either agent alone in trastuzumab sensitive breast cancer. [Table: see text]


2019 ◽  
Vol 17 (3) ◽  
pp. 720-730 ◽  
Author(s):  
Veronica Garcia-Carpizo ◽  
Sergio Ruiz-Llorente ◽  
Jacinto Sarmentero ◽  
Ana González-Corpas ◽  
Maria J. Barrero

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