Selective toxicity of TGF-alpha-PE40 to EGFR-positive cell lines: selective protection of low EGFR-expressing cell lines by EGF.

The sensitivity of human breast and lung cancer cell lines to TGF-alpha-PE40, a novel chimeric recombinant cytotoxin composed of two independent domains, (i) TGF-alpha and (ii) a 40 kDa segment of the Pseudomonas exotoxin protein, PE-40, was investigated. Toxicity varied widely, correlated with epid...

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Autores principales: Kirk, J., Carmichael, J., Stratford, I. J., Harris, A. L.
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 1994
Materias:
Research Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1969441/
https://www.ncbi.nlm.nih.gov/pubmed/8198991
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author Kirk, J.
Carmichael, J.
Stratford, I. J.
Harris, A. L.
author_facet Kirk, J.
Carmichael, J.
Stratford, I. J.
Harris, A. L.
author_sort Kirk, J.
collection PubMed
description The sensitivity of human breast and lung cancer cell lines to TGF-alpha-PE40, a novel chimeric recombinant cytotoxin composed of two independent domains, (i) TGF-alpha and (ii) a 40 kDa segment of the Pseudomonas exotoxin protein, PE-40, was investigated. Toxicity varied widely, correlated with epidermal growth factor receptor (EGFR) levels (P = 0.01) and was greatly reduced by EGF, indicating that binding of TGF-alpha-PE40 to EGFR is important in mediating toxicity. Cell lines expressing low EGFR levels were most highly protected by EGF, indicating that normal (low EGFR-expressing) tissue may be selectively protected by EGF in vivo. P-glycoprotein did not confer resistance to TGF-alpha-PE40, and toxicity was unaffected by multidrug resistance-modulating agents (cyclosporin A, tamoxifen, verapamil), indicating a role for TGF-alpha-PE40 in the clinical management of drug-resistant tumours.
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spelling pubmed-19694412009-09-10 Selective toxicity of TGF-alpha-PE40 to EGFR-positive cell lines: selective protection of low EGFR-expressing cell lines by EGF. Kirk, J. Carmichael, J. Stratford, I. J. Harris, A. L. Br J Cancer Research Article The sensitivity of human breast and lung cancer cell lines to TGF-alpha-PE40, a novel chimeric recombinant cytotoxin composed of two independent domains, (i) TGF-alpha and (ii) a 40 kDa segment of the Pseudomonas exotoxin protein, PE-40, was investigated. Toxicity varied widely, correlated with epidermal growth factor receptor (EGFR) levels (P = 0.01) and was greatly reduced by EGF, indicating that binding of TGF-alpha-PE40 to EGFR is important in mediating toxicity. Cell lines expressing low EGFR levels were most highly protected by EGF, indicating that normal (low EGFR-expressing) tissue may be selectively protected by EGF in vivo. P-glycoprotein did not confer resistance to TGF-alpha-PE40, and toxicity was unaffected by multidrug resistance-modulating agents (cyclosporin A, tamoxifen, verapamil), indicating a role for TGF-alpha-PE40 in the clinical management of drug-resistant tumours. Nature Publishing Group 1994-06 /pmc/articles/PMC1969441/ /pubmed/8198991 Text en https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/.
spellingShingle Research Article
Kirk, J.
Carmichael, J.
Stratford, I. J.
Harris, A. L.
Selective toxicity of TGF-alpha-PE40 to EGFR-positive cell lines: selective protection of low EGFR-expressing cell lines by EGF.
title Selective toxicity of TGF-alpha-PE40 to EGFR-positive cell lines: selective protection of low EGFR-expressing cell lines by EGF.
title_full Selective toxicity of TGF-alpha-PE40 to EGFR-positive cell lines: selective protection of low EGFR-expressing cell lines by EGF.
title_fullStr Selective toxicity of TGF-alpha-PE40 to EGFR-positive cell lines: selective protection of low EGFR-expressing cell lines by EGF.
title_full_unstemmed Selective toxicity of TGF-alpha-PE40 to EGFR-positive cell lines: selective protection of low EGFR-expressing cell lines by EGF.
title_short Selective toxicity of TGF-alpha-PE40 to EGFR-positive cell lines: selective protection of low EGFR-expressing cell lines by EGF.
title_sort selective toxicity of tgf-alpha-pe40 to egfr-positive cell lines: selective protection of low egfr-expressing cell lines by egf.
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1969441/
https://www.ncbi.nlm.nih.gov/pubmed/8198991
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