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.
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.
Danova
M
M
Dipartimento di Medicina Interna e Terapia Medica, I.R.C.C.S. Policlinico San Matteo, University of Pavia, Italy.
Pellicciari
C
C
Zibera
C
C
Mangiarotti
R
R
Gibelli
N
N
Giordano
M
M
Wang
E
E
Mazzini
G
G
Riccardi
A
A
D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000473:pathology*; D001973:Bromodeoxyuridine; D002453:Cell Cycle / Q000187:drug effects*; D018797:Cell Cycle Proteins; D002460:Cell Line; D004273:DNA, Neoplasm / Q000032:analysis / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D019394:Ki-67 Antigen; D007700:Kinetics; D009363:Neoplasm Proteins / Q000032:analysis* / Q000096:biosynthesis; D009687:Nuclear Proteins / Q000032:analysis* / Q000096:biosynthesis; D020648:Peptide Elongation Factor 1; D018809:Proliferating Cell Nuclear Antigen; D014176:Protein Biosynthesis; D011506:Proteins / Q000032:analysis*; D013629:Tamoxifen / Q000633:toxicity*; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D004273:DNA, Neoplasm; C503234:EEF1A2 protein, human; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D020648:Peptide Elongation Factor 1; D018809:Proliferating Cell Nuclear Antigen; D011506:Proteins; D013629:Tamoxifen; D001973:Bromodeoxyuridine