TY - JOUR
T1 - Inhibition of estrogen- and growth factor-induced proliferation of human breast cancer cell lines by TCDD
T2 - characterization and mechanistic studies
AU - Safe, S.
AU - Biegel, L.
AU - Harris, M.
AU - Narasimhan, T. R.
AU - Lui, H.
AU - Fernandez, P.
PY - 1992/7
Y1 - 1992/7
N2 - 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.
AB - 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.
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U2 - 10.1016/0045-6535(92)90485-A
DO - 10.1016/0045-6535(92)90485-A
M3 - Article
AN - SCOPUS:0026666617
SN - 0045-6535
VL - 25
SP - 83
EP - 86
JO - Chemosphere
JF - Chemosphere
IS - 1-2
ER -