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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.

Original publication

DOI

10.1038/bjc.1994.194

Type

Journal article

Journal

Br J Cancer

Publication Date

06/1994

Volume

69

Pages

988 - 994

Keywords

Breast Neoplasms, Carcinoma, Non-Small-Cell Lung, Carcinoma, Small Cell, Cell Division, Cell Line, Cyclosporine, Dose-Response Relationship, Drug, Drug Interactions, Epidermal Growth Factor, ErbB Receptors, Exotoxins, Female, Humans, Lung Neoplasms, Recombinant Fusion Proteins, Recombinant Proteins, Tamoxifen, Transforming Growth Factor alpha, Tumor Cells, Cultured, Verapamil