Transformation of MCF-10A Human Breast Epithelial Cells by Zeranol and Estradiol-17β

Abstract:  Among the endocrine factors associated with breast cancer, estrogens are considered to play a central role in human breast carcinogenesis. Breast cancer risks are increased by long-term exposure to estrogens. Zeranol (Ralgro) is a nonsteroidal agent with estrogenic activity that is used as a growth promoter in the U.S. beef and veal industry. To determine whether zeranol and estradiol-17β play a role in the neoplastic transformation of human breast and to compare the estrogenic potency of zeranol to that of estradiol-17β in human breast, we treated human breast epithelial cell MCF-10A with different doses of zeranol or estradiol-17β for 10 repeated treatment cycles. By utilizing the doubling time assay, soft agar assay, and reverse transcriptase polymerase chain reaction (RT-PCR) assay, we showed that 10 repeated estradiol-17β or zeranol treatment cycles to MCF-10A cells decrease the doubling time of the cells by 30 to 40% and stimulate colony formation in soft agar and induce estrogen receptor β (ER-β) mRNA expression, all of which are not dose related in our tested dose range. Furthermore, we show that zeranol and estradiol-17β have a similar potency in the stimulation and inhibition of gene expressions in human breast cancer cell line MCF-7 by RT-PCR. These results indicate that both zeranol and estradiol-17β can induce human breast epithelial cell neoplastic transformation with similar potency in the long-term exposure through the oxidation-reduction (redox) pathway and/or ER-β-mediated pathway.