Autocrine Stimulation by Prolactin of Hormone-Responsive Breast Cancer Growth in Culture*

Abstract

Evidence obtained in human breast cancer cell lines in culture suggests that estradiol stimulates the synthesis of secretory proteins which may, in turn, mediate its mitogenic effect. We questioned whether a similar mechanism could mediate the growth-promoting effect of PRL in the N-nitrosomethylurea-induced rat mammary tumor growth in soft agar, where PRL exerts a dose-dependent colony-stimulating effect. Conditioned medium obtained from PRL-treated tumors, but not from control tumors, was found to exert a significant dose-dependent colony-stimulating effect when added to N-nitrosomethylurea-induced mammary tumors plated in soft agar under serum-free medium conditions. The growth-promoting action of conditioned medium from PRL-treated tumors was abolished by pretreatment with heat, trypsin, and Concanavalin-A, suggesting the possible glycoprotein nature of the oPRL-induced growth factor(s). These results provide support for the novel hypothesis that estradiol and PRL may support the growth of hormone-responsive breast cancer through a similar mechanism.