Down-regulation of the Epidermal Growth Factor Receptor by Altering N-Glycosylation: Emerging Role of β1,4-Galactosyltransferases

Background/Aim: Blocking N-glycosylation of the epidermal growth factor receptor (EGER) by tunicanzycin inhibits its cellular accumulation. Due to the toxic potential of this drug, finding less drastic routes to reduce EGFR expression is desirable. Materials and Methods: Four glycosylation mutants of Chinese hamster ovary (CHO) cells with defects in N-glycan processing and branch-end maturation were tested for EGFR gene expression, production, functionality and routing after transfection with a vector encoding for human EGFR. Results: Lack of conversion of paucimannosidic to hybrid/complex-type N-glycans and drastic reductions in sialylationlgalactosylation did not lead to major effects. In contrast, EGFR expression in a mutant with reduced presence of beta 1,4-galactosyltransferases-I-VI was markedly reduced. Misrouting or defects in transfectionl transcription were excluded. Conclusion: beta 1,4-Galactosyltransferases warrant for further attention as effector(s) in order to attenuate EGFR-dependent signaling.