Stimulation of PC cell-derived growth factor (epithelin/granulin precursor) expression by estradiol in human breast cancer cells

PC cell-derived growth factor (PCDGF) is an 88 kDa glycosylated protein isolated from a highly tumorigenic mouse teratoma derived cell line which is similar to the epithelin/granulin precursor. Using Northern blot and western blot analyses, we detect the expression of PCDGF mRNA and protein in MCF-7 human breast cancer cells. We show that 17-beta-estradiol stimulates PCDGF mRNA and protein expression in a time and dose-dependent manner. The stimulation of PCDGF expression by 17-beta-estradiol was observed as early as 4 hours and reached a maximum at 12 hours. Maximal stimulation of PCDGF mRNA and protein expression by 17-beta-estradiol was observed at a concentration of 10(-8) M. The stimulation of PCDGF expression by 17-beta-estradiol was completely inhibited by treatment with actinomycin D and with the antiestrogen 4-hydroxytamoxifen. The stimulation of PCDGF expression was also demonstrated in another human estrogen-responsive cell line T47D. The results presented here provide evidence of a novel estradiol responsive gene product in human breast cancer cell lines and give information about the hormonal control of epithelin/granulin (PCDGF) expression in these cells. (C) 1999 Academic Press.