Hormonal regulation of synthesis and secretion of pS2 protein relevant to growth of human breast cancer cells (MCF-7).

We have recently identified human epidermal growth factor-like immunoreactive factor synthesized and secreted by human breast cancer cells (MCF-7) as a secretory protein encoded by the pS2 gene, the transcription of which is directly induced by estrogen. We demonstrated in this paper that synthesis and secretion of pS2 protein as well as pS2 mRNA were induced about 5-fold specifically by physiological concentrations of estrogen, which stimulated growth of the cells about 5-fold. Stimulative effects of estrogen on both cell growth and synthesis/secretion of pS2 protein were inhibited completely by actinomycin D, cycloheximide, and antiestrogen. However, the increase in DNA synthesis from 6 h after the start of treatment of the cells with estrogen preceded the increase in the amount of pS2 protein in the culture medium from 12 h after that. Furthermore purified pS2 protein did not stimulate DNA synthesis of the cells. These results suggest that induction of pS2 protein by estrogen is not involved in the growth-stimulating effect of estrogen in MCF-7 cells.