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-beta). We isolated variants of MCF-7 highly resistant to TGF-beta. 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.
D001943:Breast Neoplasms / Q000473:pathology*; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D009363:Neoplasm Proteins / Q000032:analysis; D010455:Peptides / Q000494:pharmacology*; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D015291:Transforming Growth Factors; D014407:Tumor Cells, Cultured / Q000187:drug effects
D004967:Estrogens; D009363:Neoplasm Proteins; D010455:Peptides; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D015291:Transforming Growth Factors