Synthetic murine epidermal growth factor sequence 20-31 is mitogenic and angiogenic.
Epidermal growth factor (EGF) and its homologue, transforming growth factor alpha (TGF alpha), are mitogenic, angiogenic and tumour-promoting polypeptides. Much effort has therefore been directed towards the development of EGF/TGF alpha antagonists as a potential cancer therapy. Initial reports that some EGF/TGF alpha synthetic fragments possess EGF-receptor binding activity have not been confirmed in subsequent studies. We have found, however, that the murine EGF B-loop sequence: Ac-[(S-acetamidomethyl)-Cys20,31]-EGF-(20-31)-NH2 [(mEGF-(20-31)] produces biological effects consistent with the parent molecule in bovine, murine, chick and human, but not rat, model systems. In parallel experiments, both mEGF and mEGF-(20-31) elicit migratory, cytoprotective, growth-stimulatory, growth-inhibitory and angiogenic responses. The reverse B-loop sequence, mEGF-(31-20), is also mitogenic and angiogenic. The C-loop sequence, mEGF-(33-42), has no mitogenic or angiogenic activity when applied alone, does not block the mitogenic effect of mEGF, but does block the angiogenic effect of mEGF. It has not been established that the EGF receptor is the target for these fragments, but the results suggest that the residual biological activities of EGF fragments merit further investigation.
Nelson
J
J
School of Biology and Biochemistry, Queen's University of Belfast, UK.
Stewart
R
R
McGivern
M
M
Bailie
J R
JR
Walker
B
B
Murphy
R F
RF
Wilson
D J
DJ
D016475:3T3 Cells / Q000166:cytology / Q000187:drug effects; D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D008934:Mitogens / Q000494:pharmacology*; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D010446:Peptide Fragments / Q000009:adverse effects / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D008934:Mitogens; D010446:Peptide Fragments; D004815:Epidermal Growth Factor