title: Molecular response of 4T1-induced mouse mammary tumours and healthy tissues to zinc treatment.
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.
authors: Department of Pathological Physiology, Faculty of Medicine, Masaryk University, CZ-625 00 Brno, Czech Republic.
authors: Marketa
authors: M
authors: Sztalmachova
authors: Department of Pathological Physiology, Faculty of Medicine, Masaryk University, CZ-625 00 Brno, Czech Republic.
authors: Jaromir
authors: J
authors: Gumulec
authors: Department of Pathological Physiology, Faculty of Medicine, Masaryk University, CZ-625 00 Brno, Czech Republic.
authors: Martina
authors: M
authors: Raudenska
authors: Department of Pathological Physiology, Faculty of Medicine, Masaryk University, CZ-625 00 Brno, Czech Republic.
authors: Hana
authors: H
authors: Polanska
authors: Department of Pathological Physiology, Faculty of Medicine, Masaryk University, CZ-625 00 Brno, Czech Republic.
authors: Monika
authors: M
authors: Holubova
authors: Department of Pathological Physiology, Faculty of Medicine, Masaryk University, CZ-625 00 Brno, Czech Republic.
authors: Jan
authors: J
authors: Balvan
authors: Department of Pathological Physiology, Faculty of Medicine, Masaryk University, CZ-625 00 Brno, Czech Republic.
authors: Kristyna
authors: K
authors: Hudcova
authors: Department of Experimental Biology, Faculty of Science, Masaryk University, CZ-625 00 Brno, Czech Republic.
authors: Lucia
authors: L
authors: Knopfova
authors: Central European Institute of Technology, Brno University of Technology, CZ-616 00 Brno, Czech Republic.
authors: Rene
authors: R
authors: Kizek
authors: Central European Institute of Technology, Brno University of Technology, CZ-616 00 Brno, Czech Republic.
authors: Vojtech
authors: V
authors: Adam
authors: Department of Physiology, Faculty of Medicine, Masaryk University, CZ-625 00 Brno, Czech Republic.
authors: Petr
authors: P
authors: Babula
authors: Department of Pathological Physiology, Faculty of Medicine, Masaryk University, CZ-625 00 Brno, Czech Republic.
authors: Michal
authors: M
authors: Masarik
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D008099:Liver / Q000378:metabolism; D008668:Metallothionein / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D014157:Transcription Factors / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays; D019287:Zinc Sulfate / Q000008:administration & dosage* / Q000494:pharmacology; D000097809:Transcription Factor MTF-1
chemical_list: D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D008668:Metallothionein; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D019287:Zinc Sulfate; D000097809:Transcription Factor MTF-1