Hormone responsive human breast cancer in long-term tissue culture: effect of insulin.

Abstract
The mechanisms of steroid and peptide hormone action in human breast cancer are poorly understood. A cell line of human breast cancer in long-term tissue culture that possesses various steroid hormone receptors and responses was previously characterized, providing a model for the study of steroid hormone action. The present studies describe a human breast cancer [MCF-7] in vitro that responds to physiologic concentrations of insulin with an increased rate of macromolecular synthesis and growth. Thymidine and uridine incorporation in cells in serum free medium are stimulated by 10-11 M insulin and are maximal with 10-8 M. Leucine incorporation is stimulated by 5 .times. 10-11 M insulin and is maximal with 10-9 M. Significant stimulation of uridine and leucine incorporation is evident by 3 h and maximal by 10 h. A 10 h lag period exists for insulin stimulation of thymidine incorporation, which is maximal from 14-24 h. The effect of 10-8 M insulin on macromolecular synthesis is accompanied by a 69% increase above controls in the number of cells after 24 h. The effect on macromolecular synthesis is observed in glucose free medium. Insulin''s effect on protein synthesis is not blocked by inhibition of RNA synthesis with actinomycin D. Glucocorticoids partially inhibit the action of insulin in these cells. This system provides a model for studying insulin action and suggests that some human breast cancer may show growth regulation by insulin.