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Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on growth factor expression in the human breast cancer cell line MCF-7
1Heinrich-Heine University of Düsseldorf, Department of Toxicology, Düsseldorf, Germany.
Abstract:
The aim of this study was to examine whether changes in growth factor or cytokine expression could be responsible for the growth inhibitory effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the human breast cancer MCF-7 cell line. Treatment of MCF-7 cells with 10 nM TCDD for 7 days reduced the cell growth to 60% of control; this effect was partly abolished by cotreatment of the cells with 100 nM 17 beta-estradiol (E2). The inhibition of cell growth by TCDD was accompanied by an enhanced secretion of transforming growth factor-beta (TGF-beta) and the TGF-beta content in cell culture supernatants was 2-fold higher than in controls. Using reverse transcription polymerase chain reaction (RT-PCR), the effect of TCDD on the expression of TGF-beta isoforms, transforming growth factor-alpha (TGF-alpha), tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) was investigated. It was demonstrated that incubation with 1, 10 and 100 nM TCDD for 24 h increased mRNA levels of TGF-alpha, TNF-alpha and IL-1 beta. The strongest effect was found on IL-1 beta, the mRNA level of which was dose-dependently increased. TCDD had a minor effect on TGF-alpha and TNF-alpha mRNA. The mRNA levels were significantly increased after treatment with 10 and 100 nM TCDD. The mRNA expression of TGF-beta 1 and TGF-beta 2 was unchanged, whereas the TGF-beta 3 mRNA level was enhanced 2 to 3-fold after TCDD treatment. From the results, we suggest that TCDD-induced growth inhibition in MCF-7 cells is related to the growth inhibitory action of a set of growth factors and cytokines which have a contextual action on MCF-7 cell proliferation.
Insights
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) inhibits human breast cancer cell growth by altering growth factor and cytokine expression. TCDD increases transforming growth factor-beta (TGF-beta) secretion and modifies mRNA levels of TGF-alpha, TNF-alpha, and IL-1 beta.
Area of Science:
- Environmental Toxicology
- Molecular Biology
- Cancer Research
Background:
- 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a potent environmental toxin.
- TCDD is known to affect various cellular processes, including cell proliferation.
- The human breast cancer MCF-7 cell line is a common model for studying estrogen-dependent breast cancer.
Purpose of the Study:
- To investigate the role of growth factor and cytokine expression in TCDD-induced growth inhibition of MCF-7 cells.
- To determine the effect of TCDD on the secretion and mRNA levels of specific growth factors and cytokines.
Main Methods:
- MCF-7 cells were treated with varying concentrations of TCDD and 17 beta-estradiol (E2).
- Cell growth was assessed after 7 days of treatment.
- Transforming growth factor-beta (TGF-beta) secretion was measured in cell culture supernatants.
- Reverse transcription polymerase chain reaction (RT-PCR) was used to analyze mRNA expression of TGF-beta isoforms, TGF-alpha, TNF-alpha, and IL-1 beta.
Main Results:
- TCDD (10 nM) significantly inhibited MCF-7 cell growth by 40%, an effect partially reversed by E2.
- TCDD treatment led to a 2-fold increase in TGF-beta secretion.
- TCDD upregulated mRNA levels of TGF-alpha, TNF-alpha, and IL-1 beta, with IL-1 beta showing a dose-dependent increase.
- TCDD treatment increased TGF-beta 3 mRNA levels 2-3 fold, while TGF-beta 1 and TGF-beta 2 mRNA remained unchanged.
Conclusions:
- TCDD-induced growth inhibition in MCF-7 cells is associated with altered expression of growth factors and cytokines.
- The observed changes in TGF-beta, TGF-alpha, TNF-alpha, and IL-1 beta likely contribute to the anti-proliferative effects of TCDD.
- These findings highlight the complex interplay between environmental toxins and cellular signaling pathways in breast cancer progression.