INTERACTION OF 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN AND RETINOIC ACID IN MCF-7 HUMAN BREAST-CANCER CELLS

Both retinoic acid (RA) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) elicit a number of common biochemical and toxic responses including teratogenic effects in mice and inhibition of cell proliferation of numerous cell lines. In mice, RA plus TCDD interact synergistically as teratogens, suggesting a link between the RA and aryl hydrocarbon receptor signal transduction pathways. In this study, it was shown that both RA and TCDD elicit a number of common responses in MCF-7 human breast cancer cells, including inhibition of estrogen-induced cell proliferation and [H-3]thymidine uptake, inhibition of nuclear estrogen receptor (ER) ligand binding, and interactions with a consensus [(32)]estrogen-responsive element in a gel mobility shift assay. RA and TCDD also decrease steady-state ER mRNA levels in a time-dependent manner. Moreover, interactive studies in which cells were treated with both RA plus TCDD also resulted in decreased responses. (C) 1994 Academic Press, Inc.