Development of an Epidermal Growth Factor Derivative with EGFR Blocking Activity
dc.contributor.author
dc.date.accessioned
2013-09-20T06:22:11Z
dc.date.available
2013-09-20T06:22:11Z
dc.date.issued
2013
dc.identifier.uri
dc.description.abstract
The members of the epidermal growth factor (EGF)/ErbB family are prime targets for cancer therapy. However, the therapeutic efficiency of the existing anti-ErbB agents is limited. Thus, identifying new molecules that inactivate the ErbB receptors through novel strategies is an important goal on cancer research. In this study we have developed a shorter form of human EGF (EGFt) with a truncated C-terminal as a novel EGFR inhibitor. EGFt was designed based on the superimposition of the three-dimensional structures of EGF and the Potato Carboxypeptidase Inhibitor (PCI), an EGFR blocker previously described by our group. The peptide was produced in E. coli with a high yield of the correctly folded peptide. EGFt showed specificity and high affinity for EGFR but induced poor EGFR homodimerization and phosphorylation. Interestingly, EGFt promoted EGFR internalization and translocation to the cell nucleus although it did not stimulate the cell growth. In addition, EGFt competed with EGFR native ligands, inhibiting the proliferation of cancer cells. These data indicate that EGFt may be a potential EGFR blocker for cancer therapy. In addition, the lack of EGFR-mediated growth-stimulatory activity makes EGFt an excellent delivery agent to target toxins to tumours over-expressing EGFR
dc.format.mimetype
application/pdf
dc.language.iso
eng
dc.publisher
Public Library of Science
dc.relation.isformatof
Reproducció digital del document publicat a: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0069325
dc.relation.ispartof
PLoS ONE, 2013, vol. 8, núm. 7, p. e69325
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Articles publicats (D-B)
dc.rights
Attribution 3.0 Spain
dc.rights.uri
dc.subject
dc.title
Development of an Epidermal Growth Factor Derivative with EGFR Blocking Activity
dc.type
info:eu-repo/semantics/article
dc.rights.accessRights
info:eu-repo/semantics/openAccess
dc.embargo.terms
Cap
dc.type.version
info:eu-repo/semantics/publishedVersion
dc.identifier.doi
dc.identifier.idgrec
018314
dc.identifier.eissn
1932-6203