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Cell Cycle Kinetic Effects of Tamoxifen on Human Breast Cancer Cells
Author(s) -
DANOVA MARCO,
PELLICCIARI CARLO,
ZIBERA CARLO,
MANGIAROTTI ROSANNA,
GIBELLI NADIA,
GIORDANO MONICA,
WANG EUGENIA,
MAZZINI GIULIANO,
RICCARDI ALBERTO
Publication year - 1993
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1993.tb17206.x
Subject(s) - cell cycle , proliferating cell nuclear antigen , flow cytometry , cell growth , dna synthesis , bromodeoxyuridine , chemistry , cancer cell , cell , tamoxifen , mcf 7 , cancer research , biology , microbiology and biotechnology , medicine , cancer , breast cancer , dna , human breast , biochemistry
Tamoxifen is known to inhibit the growth of some human mammary carcinoma cells; this effect is accompanied by a decrease in the proportion of cells synthesizing DNA. In this work, flow cytometry of DNA and of bromodeoxyuridine labeling and the evaluation of the cell cycle-related antigens Ki-67, PCNA, and statin were used to investigate the changes in the proliferation kinetics of MCF-7 cells before and after treatment with 10(-7) M TAM. The treatment with TAM induced a significant decrease in the fraction of S-phase cells and an increase in those with a DNA content typical of G0/1 phase. The TAM-induced block in G0/1 is paralleled by a decrease in the frequency of cells expressing Ki-67 and PCNA, and by an increase in statin-positive (G0) cells. These results confirmed that the TAM-induced inhibition of cell growth is associated with major changes in the cell cycle parameters of MCF-7 cells, and provide the first experimental evidence that two main mechanisms are operating: the accumulation of cells in G1, before the onset of S-phase, and the exit of some cells from the cycling compartment.