Molecular response of 4T1-induced mouse mammary tumours and healthy tissues to zinc treatment

Sztalmachova,Marketa; Gumulec,Jaromir; Raudenska,Martina; Polanska,Hana; Holubova,Monika; Balvan,Jan; Hudcova,Kristyna; Knopfova,Lucia; Kizek,Rene; Adam,Vojtech; Babula,Petr; Masarik,Michal

doi:10.3892/ijo.2015.2883

Molecular response of 4T1-induced mouse mammary tumours and healthy tissues to zinc treatment

Authors:
- Marketa Sztalmachova
- Jaromir Gumulec
- Martina Raudenska
- Hana Polanska
- Monika Holubova
- Jan Balvan
- Kristyna Hudcova
- Lucia Knopfova
- Rene Kizek
- Vojtech Adam
- Petr Babula
- Michal Masarik
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Affiliations: Department of Pathological Physiology, Faculty of Medicine, Masaryk University, CZ-625 00 Brno, Czech Republic, Department of Experimental Biology, Faculty of Science, Masaryk University, CZ-625 00 Brno, Czech Republic, Central European Institute of Technology, Brno University of Technology, CZ-616 00 Brno, Czech Republic, Department of Physiology, Faculty of Medicine, Masaryk University, CZ-625 00 Brno, Czech Republic
Published online on: February 9, 2015 https://doi.org/10.3892/ijo.2015.2883
Pages: 1810-1818

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Abstract

Breast cancer patients negative for the nuclear oestrogen receptor α have a particularly poor prognosis. Therefore, the 4T1 cell line (considered as a triple-negative model) was chosen to induce malignancy in mice. The aim of the present study was to assess if zinc ions, provided in excess, may significantly modify the process of mammary oncogenesis. Zn(II) ions were chosen because of their documented antitumour effects. Zn(II) is also known to induce the expression of metallothioneins (MT) and glutathion (GSH). A total dose of zinc sulphate per one gram of mouse weight used in the experiment was 0.15 mg. We studied the expression of MT1, MT2, TP53 and MTF-1 genes and also examined the effect of the tumour on antioxidant capacity. Tumour-free mice had significantly higher expression levels of the studied genes (p<0.003). Significant differences were also revealed in the gene expression between the tissues (p<0.001). The highest expression levels were observed in the liver. As compared to brain, lung and liver, significantly lower concentrations of MT protein were found in the primary tumour; an inverse trend was observed in the concentration of Zinc(II). In non-tumour mice, the amount of hepatic hydrosulphuryl groups significantly increased by the exposure to Zn(II), but the animals with tumour induction showed no similar trend. The primary tumour size of zinc-treated animals was 20% smaller (p=0.002); however, no significant effect on metastasis progression due to the zinc treatment was discovered. In conclusion, Zn(II) itself may mute the growth of primary breast tumours especially at their early stages.

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