Oestrogen-responsive human breast cancer in long term tissue culture

Marc E. Lippman, Gail Bolan

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Abstract

Four human breast cancer cell lines, MCF7, HT39, Kielty and G11, established in culture, show oestrogen dependence in vitro, similar to in vivo circumstances. MCF7 cells responded to oestrogen treatment in vitro by increased thymidine (TdR) incorporation: 10-8 M oestradiol doubled TdR uptake, while 5x10-6 M oestradiol inhibited the cells below control levels. Diethylstilboestrol stimulated these cells as effectively as oestradiol at 10-8 M, and inhibited them at more than 5x10-7 M. The effect of the antioestrogen ICI46,474 (Tamoxifen) on macromolecular syntheses (DNA, protein) was reversed by oestradiol addition, showing the hormone dependence of these cells. Tamoxifen killed the cells after 4 days' treatment, but resistant colonies could survive which were hormone independent. Tamoxifen inhibited these cells primarily by interfering with the trophic effects of oestrogen. Tamoxifen binds to oestradiol receptors with about a 1000 fold lower affinity. The MCF7 line has been maintained for 2 years in culture and is a valuable tool for studies of the steroid hormone action. The other 3 cell lines were not stimulated by low doses of oestradiol, nor were they inhibited by Tamoxifen but were killed by oestradiol at 10-5 M. The inhibitory oestrogen doses can be readily achieved in patients with metastatic breast cancer. It would explain why some tumours are stimulated at physiological doses while others are destroyed at higher doses of oestrogens. (Sugar - Budapest)

Original languageEnglish (US)
Pages (from-to)592-593
Number of pages2
JournalNature
Volume256
Issue number5518
DOIs
StatePublished - Dec 1 1975

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