Overexpression of metallothionein confers resistance to the cytotoxic effect of TNF with cadmium in MCF-7 breast carcinoma cells
Sciavolino, P.J.; Lee, T.H.; Vilcek, J.
Lymphokine and Cytokine Research 11(5): 265-270
1992
ISSN/ISBN: 1056-5477 PMID: 1467367 Document Number: 390113
Experiments were designed to determined whether cells that overexpress matallothionein acquire resistance to the cytotoxic action of tumor necrosis factor (TNF). Human MCF-7 mammary carcinoma cells, which are sensitive to the cytotoxic action of TNF, were stably transfected with a vector in which the human metallothionein-IIA (hMT-IIA) gene was placed under the control of the constitutively active beta-active promoter. MT-expressing clones displayed greater resistance to cadmium toxicity than control cell lines. Neither control-transfected nor MT-expressing cell lines were sensitive to the cytotoxic effect of TNF alone, even at concentrations as high asr 200 ng/ml. However, treatment of control-transfected cells with TNF in the presence of CdCl-2 produced a greater cytotoxic effect than CdCl-2 alone. MT-expressing cell clones were protected from this synergistic cytotoxic effect of TNF and CdCl-2. These results suggest that under certain condition MT expression may protect tumor cells from the cytotoxic effects of TNF.