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Multiple Sensitivities of Mammary Tumor Cells in Culture¹

Department of Hormone Biochemistry, Imperial Cancer Research Fund, Lincoln's Inn Fields, London WC2A 3PX, England

Cloned cell lines derived from the androgen-responsive Shionogi 115 mouse mammary carcinoma, when cultured in the presence of 3.5 x 10^-8 M testosterone, retain their responsiveness to testosterone and 5-dihydrotestosterone and exhibit fibroblast-like morphology; their growth is poorly regulated by cell density. Dexamethasone at 10^-8 M inhibits proliferation of these cells by 30% but stimulates them by 235% at 10^-6 M in the temporary absence of testosterone. Cell growth is little affected by serum concentration. When cultured for 3 to 4 weeks in testosterone-free medium, however, the cells lose their androgen responsiveness and retain the inhibitory but not the stimulatory response to dexamethasone. They also show an increased sensitivity to serum and increased density regulation and change to an epithelial morphology.

It is suggested that the loss of sensitivity to androgens, which does not result from absence of androgen receptor, is related in a complex way to the increased sensitivities to serum and density regulation.

¹ Presented at the John E. Fogarty International Center Conference on Hormones and Cancer, March 29 to 31, Bethesda, Md.