title: Transformation of MCF-10A human breast epithelial cells by zeranol and estradiol-17beta.
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-17beta play a role in the neoplastic transformation of human breast and to compare the estrogenic potency of zeranol to that of estradiol-17beta in human breast, we treated human breast epithelial cell MCF-10A with different doses of zeranol or estradiol-17beta 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-17beta 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 beta (ER-beta) mRNA expression, all of which are not dose related in our tested dose range. Furthermore, we show that zeranol and estradiol-17beta 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-17beta 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-beta-mediated pathway.
authors.affiliation: Laboratory of Reproductive and Molecular Endocrinology, College of Veterinary Medicine, Ohio State University, 1900 Coffey Rd., Columbus, Ohio 43210-1092, USA.
authors.forename: Suling
authors.initials: S
authors.lastname: Liu
authors.forename: Young C
authors.initials: YC
authors.lastname: Lin
mesh_terms: D001940:Breast / Q000166:cytology / Q000187:drug effects*; D001943:Breast Neoplasms / Q000209:etiology; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic; D017931:DNA Primers; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology*; D004968:Estrogens, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006801:Humans; D012313:RNA / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015029:Zeranol / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D017931:DNA Primers; D004968:Estrogens, Non-Steroidal; D004958:Estradiol; D012313:RNA; D015029:Zeranol