Growth inhibitory and antimitogenic activity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in T47D human breast cancer cells.
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 17 beta-estradiol, transforming growth factor-alpha (TGF-alpha) 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 17 beta-estradiol, EGF, TGF-alpha 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 17 beta-estradiol, TGF-alpha, 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 17 beta-estradiol. In addition, the data also show that TCDD inhibits the growth stimulatory effects of other polypeptide growth factors in T47D cells.
Fernandez
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Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station 77843-4466.
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D001943:Breast Neoplasms / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D018336:Receptors, Aryl Hydrocarbon; D011955:Receptors, Drug / Q000187:drug effects* / Q000378:metabolism; D011960:Receptors, Estrogen / Q000187:drug effects / Q000378:metabolism; D011980:Receptors, Progesterone / Q000187:drug effects / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism
D006133:Growth Substances; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D011955:Receptors, Drug; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013936:Thymidine