EGF causes hyperproliferation and apoptosis in T51B cells: involvement of high and low affinity EGFR binding sites.
We have recently described an in vitro model for liver homeostasis which involves growing T51B rat liver epithelial cells with 1 nM epidermal growth factor (EGF). There is an initial period of hyperplasia, lasting about 3 days, which is followed by an increase in apoptosis. The cell density returns to around the confluent control level 5 days after EGF addition. The dose response of T51B cells to EGF shows three distinct growth patterns. We have carried out EGF binding studies that suggest that the occupancy of the low affinity binding site of the EGF receptor, is responsible for the hyperproliferation seen when the cells are grown with high doses of EGF. These studies also suggest that the apoptosis could be triggered by down-regulation of the receptor, in a manner analogous to the removal of a trophic hormone in other systems.
Brabyn
C J
CJ
Biochemistry Department, University of Ottawa, Ontario, Canada.
Kleine
L P
LP
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001665:Binding Sites; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000008:administration & dosage / Q000494:pharmacology*; D066246:ErbB Receptors / Q000187:drug effects* / Q000378:metabolism*; D006706:Homeostasis; D066298:In Vitro Techniques; D007700:Kinetics; D008099:Liver / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D008954:Models, Biological; D051381:Rats
D004815:Epidermal Growth Factor; D066246:ErbB Receptors