INHIBITION OF ESTROGEN-INDUCED AND GROWTH FACTOR-INDUCED PROLIFERATION OF HUMAN BREAST-CANCER CELL-LINES BY TCDD - CHARACTERIZATION AND MECHANISTIC STUDIES Academic Article uri icon

abstract

  • 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 (TGF-) 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 17-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.

published proceedings

  • CHEMOSPHERE

author list (cited authors)

  • SAFE, S., BIEGEL, L., HARRIS, M., NARASIMHAN, T. R., LUI, H., & FERNANDEZ, P.

citation count

  • 3

complete list of authors

  • SAFE, S||BIEGEL, L||HARRIS, M||NARASIMHAN, TR||LUI, H||FERNANDEZ, P

publication date

  • July 1992