title: Change in metabolic turnover is an alternate mechanism increasing cell surface epidermal growth factor receptor levels in tumor cells.
abstract: The biosynthesis and metabolic turnover of the epidermal growth factor (EGF) receptor was examined in a human pancreatic carcinoma cell line, UCVA-1. This cell line has been shown to possess a much higher level of EGF receptors than is expected solely from receptor gene/mRNA dosage. Analysis of the biosynthesis using metabolic labeling, immunological quantitation, and inhibitor treatment revealed that the naked EGF receptor in UCVA-1 cells is a protein of Mr 130,000 that is matured consecutively as a Mr 160,000 and 170,000 glycoprotein through post-translational glycosylation. Analysis of the metabolic turnover using pulse-chase labeling and inhibitor treatment revealed that the rate of EGF receptor synthesis in UCVA-1 cells was similar to that in two squamous cell carcinoma cell lines, NA and Ca9-22, which also have high numbers of EGF receptors, but because of gene amplification. In contrast, the rate of receptor degradation in UCVA-1 cells was significantly slower than in the other two cell lines. These results suggest that the retarded metabolic turnover may constitute a unique mechanism for elevating cell surface EGF receptor levels in some tumor cells independent of gene amplification.
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D066246:ErbB Receptors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D005796:Genes; D006801:Humans; D007700:Kinetics; D009062:Mouth Neoplasms / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: D012333:RNA, Messenger; D066246:ErbB Receptors