Autocrine growth stimulation of the MCF 7 breast cancer cells by the estrogen-regulated 52 K protein.
The growth of MCF 7 human breast cancer cells is stimulated in vitro by estradiol (E2) and we have previously shown that estrogen-regulated glycoproteins released into the culture medium can partly mimic this effect. In this paper, we evaluate the mitogenic activity of the 52 K glycoprotein, which is a major E2-stimulated protein released by MCF 7 cells. The 52 K protein was purified 600-fold by affinity chromatography on Concanavalin A and an anti-52 K monoclonal antibody Sepharose columns. The 99% purified 52 K protein fraction stimulated the growth of estrogen-deprived MCF 7 cells. A mean 1.7-fold increase was obtained with nanomolar concentrations of seven different preparations of 52 K protein. This stimulation represented 40% of the mitogenic effect of E2. Both the 52 K protein and E2 induced microvilli at the cell surface but the effect of the 52 K protein occurred earlier. Other putative growth factors which are also stimulated by E2 and observed by [35S]cysteine labeling did not comigrate with the purified 52 K protein. Finally, the labeled 52 K protein was found to enter MCF 7 cells and to be processed into an immunoreactive 34 K protein. These data indicate that the E2-regulated 52 K glycoprotein is an autocrine mitogen on MCF 7 cells in culture and support the hypothesis that estrogens stimulate the growth of mammary cancer via this (and possibly other) secreted protein(s) acting as autocrine (and paracrine?) growth factors.
D000911:Antibodies, Monoclonal; D001943:Breast Neoplasms / Q000648:ultrastructure*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002846:Chromatography, Affinity; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D005470:Fluorometry; D006801:Humans; D008855:Microscopy, Electron, Scanning; D008970:Molecular Weight; D009363:Neoplasm Proteins / Q000494:pharmacology*; D013499:Surface Properties
D000911:Antibodies, Monoclonal; D009363:Neoplasm Proteins; C038865:estrogen regulated protein; D004958:Estradiol