| Mechanism of action of potato carboxypeptidase inhibitor (PCI) as an EGF blocker. | |
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MedLine Citation:
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PMID: 16039955 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The epidermal growth factor receptor (EGFR) signal transduction pathway plays a prominent role in the development of carcinomas, and is an interesting target for antitumoral therapy. We have previously described how potato carboxypeptidase inhibitor (PCI), a 39-amino acid protease inhibitor with a T-Knot motif, binds to EGFR receptor and inhibits the activation of receptor protein tyrosine kinase. In this paper it is shown that PCI interferes with EGFR activation through inhibition of receptor dimerization and receptor transphosphorylation induced by epidermal growth factor (EGF) and by transforming growth factor alpha (TGF-alpha). Moreover, PCI blocks the formation and activation of ErbB1/ErbB-2 heterodimers that have a prominent role in carcinoma development. As a result of these effects, PCI interferes in the EGFR signal transduction pathway by reversing the effects of EGF on the growth of two tumoral cell lines, A431 and MDA-MB-453, and promotes EGFR down-regulation. These results show that PCI acts as an EGF/TGF-alpha antagonist, which suggests its therapeutic potential in the treatment of carcinomas. |
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Authors:
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Marta Sitjà-Arnau; Miguel A Molina; Carmen Blanco-Aparicio; Laura Ferrer-Soler; Julia Lorenzo; Francesc X Avilés; Enrique Querol; Rafael de Llorens |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Cancer letters Volume: 226 ISSN: 0304-3835 ISO Abbreviation: Cancer Lett. Publication Date: 2005 Aug |
Date Detail:
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Created Date: 2005-07-25 Completed Date: 2005-09-22 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 7600053 Medline TA: Cancer Lett Country: Ireland |
Other Details:
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Languages: eng Pagination: 169-84 Citation Subset: IM |
Affiliation:
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Unitat de Bioquímica, Departament de Biologia, Facultat de Ciències, Universitat de Girona, Campus de Montilivi, 17071 Girona, Spain. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Cell Line, Tumor Cell Proliferation / drug effects Enzyme Activation / drug effects Epidermal Growth Factor / antagonists & inhibitors, drug effects* Female Humans Phosphorylation Plant Proteins / pharmacology* Protease Inhibitors / pharmacology* RNA, Messenger / analysis Receptor, Epidermal Growth Factor / drug effects Recombinant Proteins / drug effects Reverse Transcriptase Polymerase Chain Reaction Signal Transduction / drug effects* Transforming Growth Factor alpha / antagonists & inhibitors, drug effects |
| Chemical | |
Reg. No./Substance:
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0/Plant Proteins; 0/Protease Inhibitors; 0/RNA, Messenger; 0/Recombinant Proteins; 0/Transforming Growth Factor alpha; 0/carboxypeptidase inhibitor, plant; 62229-50-9/Epidermal Growth Factor; 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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