Effects of oestrogen on human breast cancer cells in culture

SynopsisOestrogen regulates the growth of human breast cancer cell lines ZR-75–1, T-47-D and MCF-7 (KO and McGrath). Basal cell growth can be reduced (T-47-D) or eliminated (ZR-75–1) by prior growth in the absence of steroid and phenol red for three weeks, demonstrating that oestrogens can have long-lasting effects on cells in culture (termed “steroid memory”). Effects of oestradiol on different cell biological parameters are described and interaction with other steroids and serum growth factors is discussed. Antioestrogen action in these cell lines is affected by at least five parameters: (1) presence of phenol red, (2) time in culture, (3) cell density, (4) antioestrogen concentration, (5) steroid memory.An in vitro model for loss of oestrogen sensitivity in breast cancer is presented. Both dependent (ZR-75–1) and responsive (T-47-D) cells lose oestrogen sensitivity when deprived of steroid in the long term but show a gradual increase in growth. For ZR-75–1 cells, the effects appear to be clonal but occur at a high frequency (about 1 in 1,000 cells). Parallel alterations in sensitivity to other steroids, antioestrogens and serum growth factors are shown. Molecular markers of this action are described and the results compared with the well-established model for loss of androgen/glucocorticoid sensitivity in SI 15 cells.