P53 mediated regulation of metalolothionen transcription in breast cancer cells
2007 (English)In: Journal of Cellular Biochemistry, ISSN 0730-2312, E-ISSN 1097-4644, Vol. 102, no 6, 1571-1583 p.Article in journal (Refereed) PublishedText
Recent studies have shown that only breast cancer epithelial cells with intact p53 can induce metallothionein (MT) synthesis after exposure to metals. In this study, the potential role of p53 on regulation of MT was investigated. Results demonstrate that zinc and copper increased metal response elements (MREs) activity and MTF-1 expression in p53 positive MN1 and parental MCF7 cells. However, inactivation of p53 by treatment with pifithrin-alpha or the presence of inactive p53 inhibited MRE-dependent reporter gene expression in response to metals. MTF-1 levels remained unchanged after treatment with zinc in cells with nonfunctional p53. The introduction of wild-type p53 in MDD2 cells, containing nonfunctional p53, enhanced the ability of zinc to increase MRE-dependent reporter gene expression. The cellular level of p21(Cip1/WAF1) was increased in MDD2 cells after p53 transfection, confirming the presence of active p53. The treatment of MN1 and parental MCF7 with trichostatin A led to a sixfold increase in the MIRE activity in response to zinc. On the contrary, MIRE activity remained unaltered in MDD2 cells with inactive p53. The above results demonstrate that activation of p53 is an important factor in metal regulation of MT.
Place, publisher, year, edition, pages
Hoboken: John Wiley & Sons, 2007. Vol. 102, no 6, 1571-1583 p.
metallothionein, p53, metal responsive elements, metal responsive transcription factor 1
Biochemistry and Molecular Biology Cell Biology
IdentifiersURN: urn:nbn:se:umu:diva-118181DOI: 10.1002/jcb.21381ISI: 000251433900021PubMedID: 17477370OAI: oai:DiVA.org:umu-118181DiVA: diva2:920657