An enzyme immunoassay for mouse epidermal growth factor utilizing a liquid phase double-antibody system

An enzyme immunoassay for mouse epidermal growth factor (EGF) involving a liquid phase double-antibody system was developed. The EGF-beta-galactosidase conjugate prepared was stable for at least 8 months. By this method, EGF was detectable at a concentration as low as 20 pg per tube. The concentrations of EGF in various tissues of mice are also presented.     

The epidermal growth factor receptor family: Biology driving targeted therapeutics

The epidermal growth factor family of receptor tyrosine kinases (ErbBs) plays essential roles in regulating cell proliferation, survival, differentiation and migration. The ErbB receptors carry out both redundant and restricted functions in mammalian development and in the maintenance of tissues in the adult mammal. Loss of regulation of the ErbB receptors underlies many human diseases, most notably cancer. Our understanding of the function and complex regulation of these receptors has fueled the development of targeted therapeutic agents for human malignancies in the last 15 years. Here we review the biology of ErbB receptors, including their structure, signaling, regulation, and roles in development and disease, then briefly touch on their increasing roles as targets for cancer therapy.     

Influence of age on epidermal growth factor receptor level in the rat brain

Summary The influence of age on¹²⁵I-epidermal growth factor (EGF) binding to rat brain plasma membranes was investigated. The specific binding of EGF to membranes decreased gradually with age in both male and female rats. There was no significant difference in the specific binding between males and females. Scatchard analysis of the binding data showed that the decrease in EGF binding with age was due to a decrease in the number of EGF receptors.     

Human papillomavirus 16 E5 up-regulates the expression of vascular endothelial growth factor through the activation of epidermal growth factor receptor, MEK/ ERK1,2 and PI3K/Akt

The E5 oncoprotein of human papillomavirus (HPV) 16 plays an important role in early cervical carcinogenesis. Vascular endothelial growth factor (VEGF) plays a central role in switching on the angiogenic phenotype during early cervical carcinogenesis. However, the relationship between E5 and VEGF has not previously been examined. To clarify the regulatory role of E5 in VEGF expression, we transferred the E5 gene into various cell types. E5 increased VEGF expression. The addition of epidermal growth factor receptor (EGFR) inhibitor significantly suppressed VEGF expression, demonstrating that E5 stimulates VEGF expression through the activation of EGFR. E5-mediated EGFR activation was accompanied by phosphorylation of Akt and ERK1/2, which are also involved in VEGF expression. Furthermore, the mRNA stability of VEGF was not affected by E5, but VEGF promoter activity could be modulated by inhibitors of the EGFR, MEK-ERK1/2 and PI3K/Akt pathways in E5-expressing cells. Collectively, these novel results suggest that HPV 16 E5 increases VEGF expression by activating EGFR, MEK/ERK1/2 and PI3K/Akt. Received 23 November 2005; received after revision 10 January 2006; accepted 9 February 2006     

N-acetylglucosaminyltransferase V modifies the signaling pathway of epidermal growth factor receptor

Transfection of sense cDNA of N-acetylglucosamyltransferase V (GnTV-S) into human H7721 hepatocarcinoma cells resulted in an increase in the N-acetylglucosamine1,6mannose1,3- branch (GnT-V product) on the N-glycans of epidermal growth factor (EGF) receptor (EGFR), and promotion of its EGF binding and tyrosine autophosphorylation, but showed little effect on the expression of EGFR protein. The phosphorylation at T308, S473 and tyrosine residue(s) and the activity of protein kinase B (Akt/PKB) as well as the phosphorylation of p42/44 mitogen-activated protein kinase (MAPK) and MAPK kinase (MEK) before and after EGF stimulation were concomitantly increased. Conversely, in the antisense GnT-V (GnTV-AS)-transfected H7721 cells, all the results were the reverse of those with GnTV-S-transfected cells. After the cells were treated with 1-deoxymannojirimycin, an inhibitor of N-glycan processing at high mannose, or antibody against the extracellular glycan domain of EGFR, the differences in PKB activity, p42/44 MAPK and MEK phosphorylation among GnTV-S-, GnTV-AS- and mock-transfected cells were significantly attenuated. These findings indicate that the altered expression of GnT-V will change the glycan structure and function of EGFR, which may modify downstream signal transduction.Received 24 March 2004; received after revision 1 May 2004; accepted 25 May 2004     

Survival of BSC-1 cells through the maintenance of cell volume brought about by epidermal growth factor depends on attachment to the substratum

Summary Addition of epidermal growth factor to culture medium without calf serum suppressed the increase in cell volume and then enhanced the survival of BSC-1 cells attached to culture dishes. However, these effects of epidermal growth factor were not observed in the case of cells on dishes coated with heat-denatured bovine serum albumin.