Estrogen Inhibits the Growth of MCF‐7 Cell Variants Resistant to Transforming Growth Factor‐beta

Human breast cancer MCF‐7 cells containing estrogen receptor are killed by transforming growth factor‐beta (TGF‐β). We isolated variants of MCF‐7 highly resistant to TGF‐β. Variants ES‐1 and ES‐4 were cloned, and the growth of ES‐1 and ES‐4 was found to be inhibited by estradiol, whereas estradiol stimulated the growth of the parental MCF‐7 cells. ES‐1 cells contained about 2‐fold higher level of estradiol receptor than MCF‐7 cells. Addition of estradiol to the culture medium for MCF‐7 and the variant changed the expression of several secreted proteins. The repertoire of secreted proteins was markedly altered in the variant. Polypeptides of molecular weight 52,000 (52 K), 65 K and 160 K were increased about 10‐ to 50‐fold in both estradiol‐treated MCF‐7 and ES‐1 cells. Polypeptide of 130 K was decreased in estradiol‐treated ES‐1 cells while this polypeptide was increased about 4‐fold in estradiol‐treated MCF‐7, as compared with untreated MCF‐7. Polypeptide of 100 K was specifically secreted in ES‐1 whether or not estradiol was present, but there appeared to be no significant amount of the 100 K protein in MCF‐7. The estradiol‐hypersensitive phenotype is discussed in relation to its aberrant expression of secreting proteins.