Overexpression of metallothionein confers resistance to the cytotoxic effect of TNF with cadmium in MCF-7 breast carcinoma cells

P. J. Sciavolino, T. H. Lee, J. Vilcek

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Experiments were designed to determine whether cells that overexpress metallothionein 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 β-actin 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 as 200 ng/ml. However, treatment of control-transfected cells with TNF in the presence of CdCl2 produced a greater cytotoxic effect than CdCl2 alone. MT-expressing cell clones were protected from this synergistic cytotoxic effect of TNF and CdCl2. These results suggest that under certain conditions MT expression may protect tumor cells from the cytotoxic effects of TNF.

Original languageEnglish
Pages (from-to)265-270
Number of pages6
JournalLymphokine and Cytokine Research
Volume11
Issue number5
Publication statusPublished - 1992 Jan 1

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Metallothionein
Cadmium
Tumor Necrosis Factor-alpha
Breast Neoplasms
Cadmium Chloride
Clone Cells
Cell Line
Actins
Genes
Neoplasms

All Science Journal Classification (ASJC) codes

  • Immunology
  • Hematology

Cite this

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abstract = "Experiments were designed to determine whether cells that overexpress metallothionein 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 β-actin 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 as 200 ng/ml. However, treatment of control-transfected cells with TNF in the presence of CdCl2 produced a greater cytotoxic effect than CdCl2 alone. MT-expressing cell clones were protected from this synergistic cytotoxic effect of TNF and CdCl2. These results suggest that under certain conditions MT expression may protect tumor cells from the cytotoxic effects of TNF.",
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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.

In: Lymphokine and Cytokine Research, Vol. 11, No. 5, 01.01.1992, p. 265-270.

Research output: Contribution to journalArticle

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AU - Sciavolino, P. J.

AU - Lee, T. H.

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N2 - Experiments were designed to determine whether cells that overexpress metallothionein 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 β-actin 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 as 200 ng/ml. However, treatment of control-transfected cells with TNF in the presence of CdCl2 produced a greater cytotoxic effect than CdCl2 alone. MT-expressing cell clones were protected from this synergistic cytotoxic effect of TNF and CdCl2. These results suggest that under certain conditions MT expression may protect tumor cells from the cytotoxic effects of TNF.

AB - Experiments were designed to determine whether cells that overexpress metallothionein 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 β-actin 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 as 200 ng/ml. However, treatment of control-transfected cells with TNF in the presence of CdCl2 produced a greater cytotoxic effect than CdCl2 alone. MT-expressing cell clones were protected from this synergistic cytotoxic effect of TNF and CdCl2. These results suggest that under certain conditions MT expression may protect tumor cells from the cytotoxic effects of TNF.

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