Cell cycle analysis of estrogen stimulation and antiestrogen inhibition of growth of the human breast cancer cell line MCF-7

Lykkesfeldt, A.E.; Larsen, J.K.; Christensen, I.J.

Breast Cancer Research and Treatment 7 Suppl: S83-S90


ISSN/ISBN: 0167-6806
PMID: 3742066
Accession: 039480018

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The human breast cancer cell line MCF-7 can be growth stimulated by estradiol (10(-8) M) when grown in the presence of high concentration of newborn calf serum (NCS, 10%) or high concentration of estrogen depleted fetal calf serum (FCS, 10%). Estradiol stimulated cultures grow with an increased growth rate and also the final cell number in the culture flasks is increased. Analysis of the cell cycle parameters revealed that the proportion of cells in the G1 phase is decreased and the proportion of S phase cells is increased. In comparison, the increase in growth fraction is less significant. These results show that estradiol stimulated cultures grow with a shorter cell cycle time and a shortening of the G1 transit time may explain the observed changes in cell cycle parameters. We assume that the shorter cell cycle time as well as the ability to grow without density inhibition may be prerequisites for tumor formation. MCF-7 cells can be growth inhibited by the antiestrogen tamoxifen (10(-6) M). The growth inhibition is estrogen reversible, but estradiol has no growth stimulatory effect under the described growth conditions (0.5% FCS). Growth inhibited cultures accumulate cells with a G1 amount of DNA and the majority of this accumulation is due to non cycling cells. Tamoxifen is not a cell cycle phase specific growth inhibitory agent since cells with a G2 amount of DNA are non cycling. Long term treatment with tamoxifen results in cell death, but a few colonies of cells survive more than 10 days' treatment.