| Cytotoxic effect of a fusion protein from transforming growth factor alpha and Pseudomonas exotoxin on rat and human bladder carcinoma cells in vitro. | |
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MedLine Citation:
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PMID: 8045915 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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A protein formed by fusion of transforming growth factor alpha with Pseudomonas exotoxin (TGF alpha-PE40) has been shown to have the ability to kill or inhibit the growth of several carcinoma cell lines. This study was designed to evaluate the in vitro cytotoxic effects of TGF alpha-PE40 on rat and human bladder carcinoma cell lines with different biological potential, and normal rat urothelial cells. The rat cell lines used were D44c, LMC19, and MYU3L, which were established in our laboratory. Human cell lines used were RT4, T24, and 253J. As a normal control, we used the first-passage culture of normal rat bladder urothelium (RU-P1). We examined the number and affinity of epidermal growth factor receptors (EGFR) in these cells, the ability of TGF alpha-PE40 to bind EGFR, and the cytotoxic effect of TGF alpha-PE40 and PE40. Rat cell lines, D44c, LMC19, and MYU3L (EGFR = 4.9 x 10(3)-11.4 x 10(3)/cell) had ED50 values (the concentration of TGF alpha-PE40 needed to reduce the viable cell population by 50%) of 180 pM, 540 pM and 6000 pM respectively; for cI (the concentration required to achieve complete inhibition of growth under continuous serum stimulation) TGF alpha-PE40 concentrations of 10(4) pM, 10(4) pM and higher than 10(4) pM respectively were required. Human cell lines, RT4, T24, and 253J (EGFR = 32 x 10(3)-126 x 10(3)/cell) had ED50 values of 20 pM, 66 pM, and 330 pM respectively and T24 showed cI values of 10(3) pM. RU-P1 (EGFR = 92.6 x 10(3)/cell) had the highest ED50 value of 8000 pM. These data indicate that the susceptibility to TGF alpha-PE40 does not always depend on the number of EGFR, that cells having a relatively small number of EGFR respond well to TGF alpha-PE40, and that normal urothelial cells are more resistant to TGF alpha-PE40 than are cancer cells. The differential effect of TGF alpha-PE40 on normal and neoplastic cells provides a rational basis for its use in vivo to control tumor growth. |
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Authors:
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S Kameyama; H Kawamata; I Pastan; R Oyasu |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Journal of cancer research and clinical oncology Volume: 120 ISSN: 0171-5216 ISO Abbreviation: J. Cancer Res. Clin. Oncol. Publication Date: 1994 |
Date Detail:
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Created Date: 1994-08-29 Completed Date: 1994-08-29 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 7902060 Medline TA: J Cancer Res Clin Oncol Country: GERMANY |
Other Details:
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Languages: eng Pagination: 507-12 Citation Subset: IM |
Affiliation:
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Department of Pathology, Northwestern University Medical School, Chicago, Illinois 60611. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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ADP Ribose Transferases* Administration, Intravesical Animals Bacterial Toxins / pharmacology Exotoxins / administration & dosage, pharmacology* Humans Pseudomonas aeruginosa Rats Receptor, Epidermal Growth Factor / metabolism Recombinant Fusion Proteins / pharmacology Transforming Growth Factor alpha / administration & dosage, genetics, pharmacology* Tumor Cells, Cultured Urinary Bladder / drug effects Urinary Bladder Neoplasms / therapy* Virulence Factors* |
| Grant Support | |
ID/Acronym/Agency:
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CA14649/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Bacterial Toxins; 0/Exotoxins; 0/Recombinant Fusion Proteins; 0/Transforming Growth Factor alpha; 0/Virulence Factors; EC 2.4.2.-/ADP Ribose Transferases; EC 2.4.2.31/toxA protein, Pseudomonas aeruginosa; EC 2.7.10.1/Receptor, Epidermal Growth Factor |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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