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Effect on Growth and Cell Cycle Kinetics of Estradiol and Tamoxifen on MCF-7 Human Breast Cancer Cells Grown in Vitro and in Nude Mice¹

University Institute of Pathological Anatomy, 11, Frederik V's Vej, Copenhagen, Denmark [N. B., K. R., M. S-T.]; Breast Cancer Section, National Cancer Institute, NIH, Bethesda, Maryland 20892 [N. B., D. B., M. E. L.]; and Department of Medicine, Finsen Institute, Copenhagen, Denmark [L. L. V.]

The effects of estradiol and tamoxifen (TAM) on the estrogen-dependent human breast cancer cell line MCF-7 grown in vitro and in nude mice were compared. The effect on growth was determined by cell number in vitro and by tumor growth curves in nude mice. The effects on the cell cycle kinetics were determined by repeated flow cytometric DNA analyses in vitro and in vivo and by the technique of labeled mitosis in nude mouse-grown tumors.

Under in vitro conditions, estradiol induced a pronounced increase in S-phase fraction and cell number. TAM inhibited growth of MCF-7 cells with a concomitant increase in the G₁ phase from 60% to 75%. In nude mice, MCF-7 only formed tumors in estradiol-supplemented mice. No differences were observed in growth and cell kinetics between 0.1 and 1.0 mg of estradiol. Daily i.p. injections of TAM resulted in tumor growth inhibition with shrinkage of tumors. The flow cytometric DNA analysis and percentage of labeled mitosis investigations revealed no significant differences in the proliferation kinetics of TAM-treated and control tumors. Calculating the cell loss factor demonstrated an increase from 69% in control tumors to 107% in TAM-treated tumors.

These experiments have shown that the cell kinetic effect of TAM is different when MCF-7 cells are grown in vitro versus in vivo. In contrast to the in vitro data, the in vivo data indicate that the growth-inhibitory effect of TAM is not mediated through a perturbation of the cell cycle.

¹ This work was supported by the Danish Cancer Society, The Thaysen Foundation, and Ruth Leyser Memorial Foundation.

² To whom requests for reprints should be addressed.

Received 12/14/87. Revised 9/ 1/88. Revised 12/15/88. Accepted 12/21/88.

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