Growth inhibitory and antimitogenic activity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in T47D human breast cancer cells

P. Fernandez, S. Safe

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

The T47D human breast cancer cells used in this study express relative high levels of the progesterone receptor (637 ±118 fmol/mg protein) and lower levels of the estrogen and aryl hydrocarbon (Ah) receptors (81 ± 3.4 and 55 ± 8.2 fmol/mg protein, respectively). Treatment of these cells with 0.1 1.0 and 10 nM concentrations of 17β-estradiol, transforming growth factor-α (TGF-α) and epidermal growth factor (EGF) resulted in concentration-dependent increase in cell proliferation and the ratios of mitogen-treated/ control cell numbers were 2.46 2.00 and 1.90, respectively. In contrast, insulin did not significantly stimulate T47D cell proliferation and insulin-like growth factor-I (IGF-I) was active only at a concentration of 10 nM. In parallel studies, the proliferative agents also stimulated the uptake of [3H]thymidine into cellular DNA. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) did not affect T47D cell growth at concentrations of 0.1 and 1.0 nM, whereas at a concentration of 10 nM a 44% decrease in cell numbers was observed. In cells cotreated with TCDD plus 100 ng/ml insulin or 10 nM 17β-estradiol, EGF, TGF-α and IGF-I, TCDD caused a concentration-dependent decrease in cell proliferation and [3H]thymidine uptake. For example, at a 10 nM concentration of TCDD there was a 32, 45, 29, 25 and 32% decrease in the 17β-estradiol, TGF-α. EGF, IGF-I and insulin-induced cell growth, respectively. These results confirm the antiproliferative activity of TCDD in T47D cells and this was similar to results previously reported in MCF-7 human breast cancer cells for the interaction of TCDD and 17β-estradiol. In addition, the data also show that TCDD inhibits the growth stimulatory effects of other polypeptide growth factors in T47D cells.

Original languageEnglish (US)
Pages (from-to)185-197
Number of pages13
JournalToxicology Letters
Volume61
Issue number2-3
DOIs
StatePublished - Jul 1992

Keywords

  • 2,3,7,8-TCDD
  • Antimitogenic activity
  • T47D cells

ASJC Scopus subject areas

  • Toxicology

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