Abstract
It has long been appreciated that mammary cancer, in both humans and experimental animals, is frequently an endocrine-responsive illness. In fact, a large number of hormonal manipulations, including ablation of ovaries, adrenals, or pituitary or additive therapies such as estrogen, progestin, androgen, or glucocorticoid administration have all been shown occasionally to induce beneficial tumor regressions. The mechanisms by which these responses are induced are largely obscure. In part, this obscurity reflects the lack of suitable model systems in which hormonal effects can be studied. Experimental animal systems are enormously complex. It is impossible to administer a hormone to an experimental animal without altering the activities or concentrations of numerous other trophic substances. In addition, it is not safe to conclude that the effects of the hormone are due to direct interactions on the target cell, as opposed to indirect effects mediated by interactions of the hormone with the immune system or supporting stroma. Thus there is an extraordinary need for human mammary cell lines of undisputed pedigree that retain hormonal responses characteristic of in vivo tissues. In addition, systems need to be provided in which hormonal effects can be studied free from the presence of unknown factors present in serum supplements. In this report we review our studies with the ZR-75–1 cell line, which is derived from a human mammary cancer (Engel et al., 1978). This cell line can be propagated indefinitely in serum-free defined medium, and exhibits striking growth dependence on the presence of insulin, 17β-estradiol, transferrin, triiodothyronine, and dexamethasone.