Inhibition of estrogen- and growth factor-induced proliferation of human breast cancer cell lines by TCDD: characterization and mechanistic studies

S. Safe, L. Biegel, M. Harris, T. R. Narasimhan, H. Lui, P. Fernandez

Research output: Contribution to journalArticle

4 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)83-86
Number of pages4
JournalChemosphere
Volume25
Issue number1-2
DOIs
StatePublished - Jul 1992

ASJC Scopus subject areas

  • Environmental Engineering
  • Environmental Chemistry
  • Chemistry(all)
  • Pollution
  • Health, Toxicology and Mutagenesis

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