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P53 mediated regulation of metallothionein transcription in breast cancer cells
Author(s) -
Ostrakhovitch Elena A.,
Olsson PerErik,
von Hofsten Jonas,
Cherian M. George
Publication year - 2007
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.21381
Subject(s) - trichostatin a , metallothionein , transfection , transcription factor , zinc , reporter gene , cancer research , biology , cancer cell , chemistry , cell culture , gene expression , microbiology and biotechnology , gene , cancer , histone , histone deacetylase , biochemistry , genetics , organic chemistry
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‐α 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 MRE activity in response to zinc. On the contrary, MRE 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. J. Cell. Biochem. 102: 1571–1583, 2007. © 2007 Wiley‐Liss, Inc.