Multiparametric assessment of the cell-cycle effects of tamoxifen on mcf-7 human breast-cancer cells
| Autor: | G. Mazzini, Maria Grazia Bottone, Carlo Pellicciari, Eugenia Wang, R. Mangiarotti, N. Gibelli, A. Riccardi, C. Zibera, M. Danova |
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| Rok vydání: | 2011 |
| Předmět: |
Cancer Research
Pathology medicine.medical_specialty medicine.diagnostic_test Cell growth Cell General Medicine Biology Cell cycle Molecular biology Flow cytometry Proliferating cell nuclear antigen chemistry.chemical_compound medicine.anatomical_structure Oncology chemistry Apoptosis Cancer cell medicine biology.protein skin and connective tissue diseases Bromodeoxyuridine |
| Zdroj: | Oncology reports. 1(4) |
| ISSN: | 1021-335X |
| Popis: | Tamoxifen (TAM)-induced changes in proliferation kinetics of the human breast cancer cell line MCF-7 were investigated using dual parameter flow cytometry (FCM) of bromodeoxyuridine (BrdU) immunolabelling and of the expression of cell-cycle related proteins (the proliferating cell nuclear antigen, PCNA, and the non proliferation-specific protein, Statin), versus the DNA content. Single-parameter FCM DNA histograms confirmed that after 96 hours of treatment with 10(-7) M TAM the fraction of S-phase cells decreased significantly, with a simultaneous accumulation of cells in the G(0)/G(1) range of DNA content. In dual-parameter FCM cytograms, the fraction of BrdU-positive cells after TAM exposure was significantly lower than in the controls, and no unlabeled S-phase cells were found. The TAM-induced block in G(0)/G(1) phase was paralleled by a decrease in the number of cells with a DNA content typical of the S-phase expressing PCNA, and by an increase in Statin-positive (G(0)) cells. Upon readdition of 10(-9) M 17 beta-estradiol (E2) to the TAM-treated cultures, BrdU-labelling as well as PCNA expression levels increased significantly, whereas the fraction of Statin-positive cells remained higher than in the controls. The results obtained confirm that the TAM-induced inhibition of cell growth is associated with major changes in the cell cycle parameters of MCF-7 cells, and provide experimental evidence that two main mechanisms are operating: the accumulation of cells in G(1), before the onset of S-phase, and the exit of some cells from the cycling compartment; however, some of those that are blocked at G(0); cannot be totally reversed by estrogens and may be permanent; These data should be taken into account in the attempt to combine the antiestrogen treatment with chemotherapy more effectively. |
| Databáze: | OpenAIRE |
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