Inhibition of estrogen- and growth factor-induced proliferation of human breast cancer cell lines by TCDD: characterization and mechanistic studies
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2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) exhibits a broad spectrum of antiestrogenic effects in estrogen receptor (ER) positive MCF-7 human breast cancer cells. The proliferation of MCF-7 cells in minimal media can also be stimulated by other mitogens, including insulin, insulin-like growth factor-1 (IGF-1), transforming growth factor α (TGF-α) and epidermal growth factor (EGF). The interactions of TCDD and these mitogens showed that TCDD inhibited growth factor-induced cell proliferation and the [3H]-thymidine uptake in the MCF-7 cells. A more detailed analysis of the interaction of TCDD and IGF-1 showed that treatment of the cells with IGF-1 (or 17ß-estradiol) caused a 100% increase in the number of membrane-bound IGF-1 receptor binding sites whereas cotreatment with TCDD completely blocked these induced effects. In contrast, the Kd values for the binding of [125I]-IGF-1 with its receptor were not significantly different in cells from all the treatment groups. Parallel studies in T47-D cells showed that there was differential-responsiveness to the proliferative effects of these mitogens; however, TCDD also exhibited comparable antimitogenic activities in these cell lines. © 1992.
author list (cited authors)
Safe, S., Biegel, L., Harris, M., Narasimhan, T. R., Lui, H., & Fernandez, P.