Cell cycle kinetic effects of tamoxifen on human breast cancer cells. Flow cytometric analyses of DNA content, BrdU labeling, Ki-67, PCNA, and statin expression

M. Danova, C. Pellicciari, C. Zibera, R. Mangiarotti, N. Gibelli, M. Giordano, E. Wang, G. Mazzini, A. Riccardi

Research output: Contribution to journalArticlepeer-review

Abstract

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 cytomctry 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 G(0/1) phase. The TAM-induced block in G(0/1) 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.

Original languageEnglish
Pages (from-to)174-181
Number of pages8
JournalAnnals of the New York Academy of Sciences
Volume698
Publication statusPublished - 1993

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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