Abstract
A chimeric toxin in which the cell binding domain of Pseudomonas exotoxin was replaced with mature human insulin-like growth factor I (IGF-I) was produced in Escherichia coli. This protein, IGF-I-PE40, was cytotoxic to human cell lines derived from a variety of tumor types, with a breast carcinoma line (MCF-7) and two hepatoma lines (HEP3B and HEPG2) showing the highest sensitivity to the toxin. The specificity of IGF-I-PE40 cytotoxicity was confirmed through competition with excess IGF-I and through blockage of toxin binding using an antibody specific to the type I IGF receptor. A potential interaction between the toxin and soluble IGF-binding proteins was also demonstrated. IGF-I-PE40 may be useful in the selective elimination of cells bearing the type I IGF receptor.
MeSH terms
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ADP Ribose Transferases*
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Animals
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Bacterial Toxins*
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Base Sequence
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Cloning, Molecular / methods
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Exotoxins / administration & dosage*
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Humans
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In Vitro Techniques
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Insulin-Like Growth Factor I / administration & dosage*
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Insulin-Like Growth Factor I / metabolism
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Mice
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Molecular Sequence Data
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Neoplasm Proteins / biosynthesis
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Oligonucleotides / chemistry
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Pseudomonas aeruginosa Exotoxin A
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Receptors, Cell Surface / metabolism*
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Receptors, Somatomedin
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Recombinant Fusion Proteins / isolation & purification
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Recombinant Fusion Proteins / toxicity
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Tumor Cells, Cultured
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Virulence Factors*
Substances
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Bacterial Toxins
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Exotoxins
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Neoplasm Proteins
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Oligonucleotides
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Receptors, Cell Surface
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Receptors, Somatomedin
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Recombinant Fusion Proteins
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Virulence Factors
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Insulin-Like Growth Factor I
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ADP Ribose Transferases